Top Reads.
Authors: PMID: 32571978 [PubMed - in process] (Source: Journal of Immunology)
Source: Journal of Immunology - June 24, 2020 Category: Allergy & Immunology Tags: J Immunol Source Type: research

New Insights into the Immune System Using Dirty Mice.
Abstract The mouse (Mus musculus) is the dominant organism used to investigate the mechanisms behind complex immunological responses because of their genetic similarity to humans and our ability to manipulate those genetics to understand downstream function. Indeed, our knowledge of immune system development, response to infection, and ways to therapeutically manipulate the immune response to combat disease were, in large part, delineated in the mouse. Despite the power of mouse-based immunology research, the translational efficacy of many new therapies from mouse to human is far from ideal. Recent data have highl...
Source: Journal of Immunology - June 24, 2020 Category: Allergy & Immunology Authors: Hamilton SE, Badovinac VP, Beura LK, Pierson M, Jameson SC, Masopust D, Griffith TS Tags: J Immunol Source Type: research

Critical Role of Intestinal Microbiota in ATF3-Mediated Gut Immune Homeostasis.
In this study, we report that both Atf3-/- and CD4creAtf3fl/fl mice displayed profound dysbiosis of gut microbiota when compared with their littermate controls. The proinflammatory Prevotella taxa, especially Prevotella copri, were more abundant in ATF3-deficient mice when compared with littermate controls. This phenotype was obviously abrogated by adoptive transfer of either TFH cells or IgA+ B cells. Importantly, depletion of gut microbiota dramatically alleviated the severity of colitis in Atf3-/- mice, whereas transfer of microbiota from Atf3-/- mice to wild-type recipients increased their susceptibility to colitis. Co...
Source: Journal of Immunology - June 22, 2020 Category: Allergy & Immunology Authors: Cao Y, Wang X, Yang Q, Deng H, Liu Y, Zhou P, Xu H, Chen D, Feng D, Zhang H, Wang H, Zhou J Tags: J Immunol Source Type: research

Eosinophil-Mediated Immune Control of Adult Filarial Nematode Infection Can Proceed in the Absence of IL-4 Receptor Signaling.
Abstract Helminth infections are accompanied by eosinophilia in parasitized tissues. Eosinophils are effectors of immunity to tissue helminths. We previously reported that in the context of experimental filarial nematode infection, optimum tissue eosinophil recruitment was coordinated by local macrophage populations following IL-4R-dependent in situ proliferation and alternative activation. However, in the current study, we identify that control of chronic adult filarial worm infection is evident in IL-4Rα-deficient (IL-4Rα-/-) mice, whereby the majority of infections do not achieve patency. An associa...
Source: Journal of Immunology - June 22, 2020 Category: Allergy & Immunology Authors: Pionnier N, Sjoberg H, Furlong-Silva J, Marriott A, Halliday A, Archer J, Steven A, Taylor MJ, Turner JD Tags: J Immunol Source Type: research

Murine Glucocorticoid Receptors Orchestrate B Cell Migration Selectively between Bone Marrow and Blood.
Abstract Glucocorticoids promote CXCR4 expression by T cells, monocytes, macrophages, and eosinophils, but it is not known if glucocorticoids regulate CXCR4 in B cells. Considering the important contributions of CXCR4 to B cell development and function, we investigated the glucocorticoid/CXCR4 axis in mice. We demonstrate that glucocorticoids upregulate CXCR4 mRNA and protein in mouse B cells. Using a novel strain of mice lacking glucocorticoid receptors (GRs) specifically in B cells, we show that reduced CXCR4 expression associated with GR deficiency results in impaired homing of mature B cells to bone marrow, wh...
Source: Journal of Immunology - June 22, 2020 Category: Allergy & Immunology Authors: Cain DW, Bortner CD, Diaz-Jimenez D, Petrillo MG, Gruver-Yates A, Cidlowski JA Tags: J Immunol Source Type: research

BCALM (AC099524.1) Is a Human B Lymphocyte-Specific Long Noncoding RNA That Modulates B Cell Receptor-Mediated Calcium Signaling.
In this study, we report the discovery and functional elucidation of a human B cell-specific lncRNA with high levels of expression in three types of B cell cancer and normal B cells. The AC099524.1 gene is upstream of the gene encoding the B cell-specific phospholipase C γ 2 (PLCG2), a B cell-specific enzyme that stimulates intracellular Ca2+ signaling in response to BCR activation. AC099524.1 (B cell-associated lncRNA modulator of BCR-mediated Ca+ signaling [BCALM]) transcripts are localized in the cytoplasm and, as expected, CRISPR/Cas9 knockout of AC099524.1 did not affect PLCG2 mRNA or protein expression. lncRNA ...
Source: Journal of Immunology - June 22, 2020 Category: Allergy & Immunology Authors: Pyfrom SC, Quinn CC, Dorando HK, Luo H, Payton JE Tags: J Immunol Source Type: research

Impact of Cysteine Residues on MHC Binding Predictions and Recognition by Tumor-Reactive T Cells.
Abstract The availability of MHC-binding prediction tools has been useful in guiding studies aimed at identifying candidate target Ags to generate reactive T cells and to characterize viral and tumor-reactive T cells. Nevertheless, prediction algorithms appear to function poorly for epitopes containing cysteine (Cys) residues, which can oxidize and form disulfide bonds with other Cys residues under oxidizing conditions, thus potentially interfering with their ability to bind to MHC molecules. Analysis of the results of HLA-A*02:01 class I binding assays carried out in the presence and absence of the reducing agent...
Source: Journal of Immunology - June 22, 2020 Category: Allergy & Immunology Authors: Sachs A, Moore E, Kosaloglu-Yalcin Z, Peters B, Sidney J, Rosenberg SA, Robbins PF, Sette A Tags: J Immunol Source Type: research

IL-25 Receptor Signaling Modulates Host Defense against Cryptococcus neoformans Infection.
In this study, we investigated the role of IL-25, one of the type 2-inducing cytokines produced by epithelial cells, in contributing to the pathogenesis of cryptococcosis. We found that pulmonary but not systemic infection with a high-virulence strain of C. neoformans significantly induced pulmonary IL-25 expression in the lungs but not brains. In response to pulmonary infection, mice deficient in the surface IL-17 receptor B, a component of the IL-25R, exhibited improved survival with a decreased brain fungal burden. The absence of IL-25R signaling diminished the type 2 and enhanced the type 1 immune response that directe...
Source: Journal of Immunology - June 19, 2020 Category: Allergy & Immunology Authors: Hansakon A, Jeerawattanawart S, Pattanapanyasat K, Angkasekwinai P Tags: J Immunol Source Type: research

Production of IL-17A at Innate Immune Phase Leads to Decreased Th1 Immune Response and Attenuated Host Defense against Infection with Cryptococcus deneoformans.
Abstract IL-17A is a proinflammatory cytokine produced by many types of innate immune cells and Th17 cells and is involved in the elimination of extracellularly growing microorganisms, yet the role of this cytokine in the host defense against intracellularly growing microorganisms is not well known. Cryptococcus deneoformans is an opportunistic intracellular growth fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired immune responses. In the current study, we analyzed the role of IL-17A in the host defense against C. deneoformans infection. IL-17A was quickly produced by &gamm...
Source: Journal of Immunology - June 19, 2020 Category: Allergy & Immunology Authors: Sato K, Yamamoto H, Nomura T, Kasamatsu J, Miyasaka T, Tanno D, Matsumoto I, Kagesawa T, Miyahara A, Zong T, Oniyama A, Kawamura K, Yokoyama R, Kitai Y, Ishizuka S, Kanno E, Tanno H, Suda H, Morita M, Yamamoto M, Iwakura Y, Ishii K, Kawakami K Tags: J Immunol Source Type: research

Soluble Uric Acid Is an Intrinsic Negative Regulator of Monocyte Activation in Monosodium Urate Crystal-Induced Tissue Inflammation.
r S Abstract Although monosodium urate (MSU) crystals are known to trigger inflammation, published data on soluble uric acid (sUA) in this context are discrepant. We hypothesized that diverse sUA preparation methods account for this discrepancy and that an animal model with clinically relevant levels of asymptomatic hyperuricemia and gouty arthritis can ultimately clarify this issue. To test this, we cultured human monocytes with different sUA preparation solutions and found that solubilizing uric acid (UA) by prewarming created erroneous results because of UA microcrystal contaminants triggering IL-1β releas...
Source: Journal of Immunology - June 19, 2020 Category: Allergy & Immunology Authors: Ma Q, Honarpisheh M, Li C, Sellmayr M, Lindenmeyer M, Böhland C, Romagnani P, Anders HJ, Steiger S Tags: J Immunol Source Type: research

Antigen Receptor Specificity and Cell Location Influence the Diversification and Selection of the B-1a Cell Pool with Age.
In this study, we demonstrate the germline-like status of phosphatidylcholine (PtC)-specific (PtC+) peritoneal B-1a cell IgM does not change with age. In direct contrast, the splenic PtC+ B-1a cell population does not preserve its IgM germline status in the aged mice. Furthermore, splenic PtC+ B-1a cells displayed more diverse variable gene segments of the H chain (VH) use in both the young and aged mice as compared with peritoneal PtC+ B-1a cells. Whereas the peritoneal PtC+ population increased VH12 use with age, we observed differential use of VH11, VH12, and VH2 between the peritoneal and splenic PtC+ populations with ...
Source: Journal of Immunology - June 19, 2020 Category: Allergy & Immunology Authors: Tsuji N, Rothstein TL, Holodick NE Tags: J Immunol Source Type: research

IL-23 Promotes a Coordinated B Cell Germinal Center Program for Class-Switch Recombination to IgG2b in BXD2 Mice.
In this study, we show that a deficiency of the p19 component of IL-23 in the autoimmune BXD2 (BXD2-p19-/- ) mouse leads to a shift of the follicular T helper cell program from follicular T helper (Tfh)-IL-17 to Tfh-IFN-γ. Although the germinal center (GC) size and the number of GC B cells remained the same, BXD2-p19-/- mice exhibited a lower class-switch recombination (CSR) in the GC B cells, leading to lower serum levels of IgG2b. Single-cell transcriptomics analysis of GC B cells revealed that whereas Ifngr1, Il21r, and Il4r genes exhibited a synchronized expression pattern with Cxcr5 and plasma cell program genes...
Source: Journal of Immunology - June 17, 2020 Category: Allergy & Immunology Authors: Hong H, Gao M, Wu Q, Yang P, Liu S, Li H, Burrows PD, Cua D, Chen JY, Hsu HC, Mountz JD Tags: J Immunol Source Type: research

P2Y6 Deficiency Enhances Dendritic Cell-Mediated Th1/Th17 Differentiation and Aggravates Experimental Autoimmune Encephalomyelitis.
In this study, we have reported that P2Y6, a member of G protein-coupled receptors, inhibits the maturation and activation of DCs via suppressing the activation of the transcription factor NF-κB. Furthermore, loss of P2Y6 does not impact T cells homeostasis in the steady-state. However, in vitro studies show that P2Y6 signaling inhibits the production of IL-12 and IL-23 and the polarization of Th1 and Th17 subsets mediated by DCs. In addition, we find that mice lacking P2Y6 develop more severe experimental autoimmune encephalomyelitis compared with wild-type mice. Our results indicate that P2Y6 functions as a pivotal...
Source: Journal of Immunology - June 17, 2020 Category: Allergy & Immunology Authors: Li Z, He C, Zhang J, Zhang H, Wei H, Wu S, Jiang W Tags: J Immunol Source Type: research

Vitamin D Regulates MerTK-Dependent Phagocytosis in Human Myeloid Cells.
In this study, we explored the effect of calcitriol on homeostatic (M-CSF, TGF-β-treated) and proinflammatory (GM-CSF-treated) human monocyte-derived macrophages and microglia using RNA sequencing. Transcriptomic analysis revealed significant calcitriol-mediated effects on both Ag presentation and phagocytosis pathways. Calcitriol downregulated MerTK mRNA and protein expression in both myeloid populations, resulting in reduced capacity of these cells to phagocytose myelin and apoptotic T cells. Proinflammatory myeloid cells expressed high levels of CYP27B1 compared with homeostatic myeloid cells. Only proinflammatory ...
Source: Journal of Immunology - June 15, 2020 Category: Allergy & Immunology Authors: Clarke J, Yaqubi M, Futhey NC, Sedaghat S, Baufeld C, Blain M, Baranzini S, Butovsky O, Antel J, White JH, Healy LM Tags: J Immunol Source Type: research

Upregulation of Multiple CD8+ T Cell Exhaustion Pathways Is Associated with Recurrent Ocular Herpes Simplex Virus Type 1 Infection.
Abstract A large proportion of the world's population harbors latent HSV type 1 (HSV-1). Cross-talk between antiviral CD8+ T cells and HSV-1 appear to control latency/reactivation cycles. We found that compared with healthy asymptomatic individuals, in symptomatic (SYMP) patients, the CD8+ T cells with the same HLA-A*0201-restricted HSV-1 epitope specificities expressed multiple genes and proteins associated to major T cell exhaustion pathways and were dysfunctional. Blockade of immune checkpoints with anti-LAG-3 and anti-PD-1 antagonist mAbs synergistically restored the frequency and function of antiviral CD8+ T ...
Source: Journal of Immunology - June 15, 2020 Category: Allergy & Immunology Authors: Coulon PG, Roy S, Prakash S, Srivastava R, Dhanushkodi N, Salazar S, Amezquita C, Nguyen L, Vahed H, Nguyen AM, Warsi WR, Ye C, Carlos-Cruz EA, Mai UT, BenMohamed L Tags: J Immunol Source Type: research

Cutting Edge: Intestinal Mucus Limits the Clonal Deletion of Developing T Cells Specific for an Oral Antigen.
In this study, we investigated whether MUC2 helps maintain CD8 T cell tolerance toward intestinal luminal Ags by gavaging wild-type and Muc2-/- mice with a model Ag and monitoring immune responses posttreatment. We report that orally delivered OVA rapidly disseminates through the blood of Muc2-/- (but not control) mice and causes immune activation of Ag-specific CD8 T cells at both local and distal sites. Further, the administration of oral OVA to Muc2-/- mice led to its presentation by thymic dendritic cells and the deletion of Ag-specific thymocytes. Collectively, our findings suggest that intestinal mucus helps limit th...
Source: Journal of Immunology - June 15, 2020 Category: Allergy & Immunology Authors: Tsai K, Huang YH, Ma C, Baldwin TA, Harder KW, Vallance BA, Priatel JJ Tags: J Immunol Source Type: research

IL-6 Deficiency Exacerbates Allergic Asthma and Abrogates the Protective Effect of Allergic Inflammation against Streptococcus pneumoniae Pathogenesis.
Abstract Allergic asthma (AA) is characterized as a Th2-biased airway inflammation that can develop lung inflammation and remodeling of the respiratory tract. Streptococcus pneumoniae is a major respiratory pathogen, causing noninvasive (otitis media and pneumonia) and invasive diseases (sepsis) in humans. We sought to determine the role of IL-6 in the regulation of lung inflammation in murine AA caused by Aspergillus fumigatus as well as its consequence on the regulation of airway barrier integrity and S. pneumoniae disease. In an AA model, IL-6 deficiency led to increased lung inflammation, eosinophil recruitmen...
Source: Journal of Immunology - June 15, 2020 Category: Allergy & Immunology Authors: Schmit T, Ghosh S, Mathur RK, Barnhardt T, Ambigapathy G, Wu M, Combs C, Khan MN Tags: J Immunol Source Type: research

Accessibility of O Antigens Shared between Salmonella Serovars Determines Antibody-Mediated Cross-Protection.
Abstract Pathogenic Salmonella serovars produce clinical manifestations ranging from systemic infection typhoid to invasive nontyphoidal Salmonella disease in humans. These serovars share a high degree of homology at the genome and the proteome level. However, whether infection or immunization with one serovar provides protection against other serovars has not been well studied. We show in this study that immunization of mice with live typhoidal serovar, Salmonella Typhi, generates cross-reactive immune responses, which provide far greater resistance against challenge with nontyphoidal serovar Salmonella Enteritid...
Source: Journal of Immunology - June 15, 2020 Category: Allergy & Immunology Authors: Ahmed A, Akhade AS, Qadri A Tags: J Immunol Source Type: research

Mice Lacking the Purinergic Receptor P2X5 Exhibit Defective Inflammasome Activation and Early Susceptibility to Listeria monocytogenes.
In this study, we report that P2X5 is a protective immune regulator during Listeria monocytogenes infection, as P2X5-deficient mice exhibit increased bacterial loads in the spleen and liver, increased tissue damage, and early (within 3-6 d) susceptibility to systemic L. monocytogenes infection. Whereas P2X5-deficient mice experience normal monocyte recruitment in response to L. monocytogenes, P2X5-deficient bone marrow-derived macrophages (BMMs) exhibit defective cytosolic killing of L. monocytogenes We further showed that P2X5 is required for L. monocytogenes-induced inflammasome activation and IL-1β production and t...
Source: Journal of Immunology - June 15, 2020 Category: Allergy & Immunology Authors: Jeong YH, Walsh MC, Yu J, Shen H, Wherry EJ, Choi Y Tags: J Immunol Source Type: research

Hypercapnia Suppresses Macrophage Antiviral Activity and Increases Mortality of Influenza A Infection via Akt1.
In this study, we show that normoxic HC increases viral replication, lung injury, and mortality in mice infected with influenza A virus (IAV). Elevated CO2 increased IAV replication and inhibited antiviral gene and protein expression in macrophages in vivo and in vitro. HC potentiated IAV-induced activation of Akt, whereas specific pharmacologic inhibition or short hairpin RNA knockdown of Akt1 in alveolar macrophages blocked HC's effects on IAV growth and the macrophage antiviral response. Our findings suggest that targeting Akt1 or the downstream pathways through which elevated CO2 signals could enhance macrophage antivi...
Source: Journal of Immunology - June 15, 2020 Category: Allergy & Immunology Authors: Casalino-Matsuda SM, Chen F, Gonzalez-Gonzalez FJ, Nair A, Dib S, Yemelyanov A, Gates KL, Budinger GRS, Beitel GJ, Sporn PHS Tags: J Immunol Source Type: research

Upregulation of Proinflammatory Bradykinin Peptides in Systemic Lupus Erythematosus and Rheumatoid Arthritis.
This study aims to investigate the biomarker potential of BK peptides, BK and BK-des-arg-9, in lupus and other rheumatic autoimmune diseases. Sera from systemic lupus erythematosus (SLE) patients and healthy subjects were screened for BK and BK-des-arg-9 by liquid chromatography-mass spectrometry metabolomics. Serum from 6-mo-old C57BL/6 mice and three murine lupus strains were also screened for the two peptides by metabolomics. Given the promising initial screening results, validation of these two peptides was next conducted using multiple reaction monitoring in larger patient cohorts. In initial metabolomics screening, B...
Source: Journal of Immunology - June 15, 2020 Category: Allergy & Immunology Authors: Vanarsa K, Henderson J, Soomro S, Qin L, Zhang T, Jordan N, Putterman C, Blanco I, Saxena R, Mohan C Tags: J Immunol Source Type: research

Cutting Edge: TNF Is Essential for Mycobacteria-Induced MINCLE Expression, Macrophage Activation, and Th17 Adjuvanticity.
In this study, we show that TNF is sufficient to upregulate MINCLE, MCL, and DECTIN-2 in macrophages. TNF signaling through TNFR1 p55 was required for upregulation of these CLR and for cytokine secretion in macrophages stimulated with the MINCLE ligand trehalose-6,6-dibehenate or infected with Mycobacterium bovis bacillus Calmette-Guérin. The Th17 response to immunization with the MINCLE-dependent adjuvant trehalose-6,6-dibehenate was specifically abrogated in TNF-deficient mice and strongly attenuated by TNF blockade with etanercept. Together, interference with production or signaling of TNF antagonized the express...
Source: Journal of Immunology - June 15, 2020 Category: Allergy & Immunology Authors: Schick J, Schäfer J, Alexander C, Dichtl S, Murray PJ, Christensen D, Sorg U, Pfeffer K, Schleicher U, Lang R Tags: J Immunol Source Type: research

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Authors: PMID: 32513873 [PubMed - in process] (Source: Journal of Immunology)
Source: Journal of Immunology - June 10, 2020 Category: Allergy & Immunology Tags: J Immunol Source Type: research

Function and Regulation of Noncanonical Caspase-4/5/11 Inflammasome.
Abstract Inflammasomes are multiprotein complexes of the innate immune system that orchestrate development of inflammation by activating the secretion of proinflammatory cytokines, IL-1β and IL-18. The LPS of Gram-negative bacteria have been shown to activate a novel, noncanonical inflammasome by directly binding in the cytosol to human caspase-4 and mouse caspase-11. Activation of noncanonical inflammasome exerts two major effects: it activates the NLRP3-caspase-1-mediated processing and secretion of IL-1β and IL-18 and induces the inflammatory cell death, pyroptosis, via gasdermin D. This previously un...
Source: Journal of Immunology - June 10, 2020 Category: Allergy & Immunology Authors: Matikainen S, Nyman TA, Cypryk W Tags: J Immunol Source Type: research

Exploiting Pre-Existing CD4+ T Cell Help from Bacille Calmette-Gu érin Vaccination to Improve Antiviral Antibody Responses.
Exploiting Pre-Existing CD4+ T Cell Help from Bacille Calmette-Guérin Vaccination to Improve Antiviral Antibody Responses. J Immunol. 2020 Jun 08;: Authors: Ng TW, Wirchnianski AS, Wec AZ, Fels JM, Johndrow CT, Saunders KO, Liao HX, Chan J, Jacobs WR, Chandran K, Porcelli SA Abstract The continuing emergence of viral pathogens and their rapid spread into heavily populated areas around the world underscore the urgency for development of highly effective vaccines to generate protective antiviral Ab responses. Many established and newly emerging viral pathogens, including HIV and Ebola viruses, ar...
Source: Journal of Immunology - June 8, 2020 Category: Allergy & Immunology Authors: Ng TW, Wirchnianski AS, Wec AZ, Fels JM, Johndrow CT, Saunders KO, Liao HX, Chan J, Jacobs WR, Chandran K, Porcelli SA Tags: J Immunol Source Type: research

Early Insights into Immune Responses during COVID-19.
Abstract Coronavirus disease-2019 (COVID-19) is caused by the newly emerged virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was recently declared as a pandemic by the World Health Organization. In its severe form, the disease is characterized by acute respiratory distress syndrome, and there are no targeted intervention strategies to treat or prevent it. The immune response is thought to both contribute to the pathogenesis of disease and provide protection during its resolution. Thus, understanding the immune response to SARS-CoV-2 is of the utmost importance for developing and testing vacci...
Source: Journal of Immunology - June 8, 2020 Category: Allergy & Immunology Authors: St John AL, Rathore APS Tags: J Immunol Source Type: research

FCRL4 Is an Fc Receptor for Systemic IgA, but Not Mucosal Secretory IgA.
In this study, we demonstrate that FCRL4 recognizes J chain-linked systemic IgA in the absence of heat aggregation. We further demonstrate that mucosal secretory IgA is not recognized by FCRL4 and that systemic IgA binding can be competitively inhibited by recombinant secretory component protein. Finally, we provide evidence that primary FCRL4-bearing human memory B cells are constitutively bound to IgA. Our study provides a mechanism for the negative regulatory activity of FCRL4 on AgR-mediated B cell activation. PMID: 32513851 [PubMed - as supplied by publisher] (Source: Journal of Immunology)
Source: Journal of Immunology - June 8, 2020 Category: Allergy & Immunology Authors: Liu Y, Goroshko S, Leung LYT, Dong S, Khan S, Campisi P, Propst EJ, Wolter NE, Grunebaum E, Ehrhardt GRA Tags: J Immunol Source Type: research

Upregulated PKM2 in Macrophages Exacerbates Experimental Arthritis via STAT1 Signaling.
In this study, Pkm2 was found to be overexpressed in ED1-positive Mφ in spleens and synovial tissues from arthritic rats via immunofluorescence, Western blotting, and quantitative RT-PCR. To reveal the role of Pkm2, Dark Agouti rats were treated with either Pkm2 enzyme inhibitor shikonin or the RNA interference plasmids of Pkm2 and negative control plasmids, respectively, via i.p. injection. Pkm2 intervention could alleviate the severity of pristane-induced arthritis in aspects of the macroscopic arthritis score, perimeter changes of midpaw, and the synovitis and destruction of the bone and cartilage as well as reduce ...
Source: Journal of Immunology - June 5, 2020 Category: Allergy & Immunology Authors: Xu J, Jiang C, Wang X, Geng M, Peng Y, Guo Y, Wang S, Li X, Tao P, Zhang F, Han Y, Ning Q, Zhu W, Meng L, Lu S Tags: J Immunol Source Type: research

Depletion of NK Cells Improves Cognitive Function in the Alzheimer Disease Mouse Model.
In this study, we report that depletion of NK cells, a type of innate lymphocytes, alleviates neuroinflammation, stimulates neurogenesis, and improves cognitive function in a triple-transgenic Alzheimer disease (AD) mouse model. NK cells in the brains of triple-transgenic AD mouse model (3xTg-AD) mice exhibited an enhanced proinflammatory profile. Depletion of NK cells by anti-NK1.1 Abs drastically improved cognitive function of 3xTg-AD mice. NK cell depletion did not affect amyloid β concentrations but enhanced neurogenesis and reduced neuroinflammation. Notably, in 3xTg-AD mice depleted of NK cells, microglia demons...
Source: Journal of Immunology - June 5, 2020 Category: Allergy & Immunology Authors: Zhang Y, Fung ITH, Sankar P, Chen X, Robison LS, Ye L, D'Souza SS, Salinero AE, Kuentzel ML, Chittur SV, Zhang W, Zuloaga KL, Yang Q Tags: J Immunol Source Type: research

Role of Aging and the Immune Response to Respiratory Viral Infections: Potential Implications for COVID-19.
Abstract Aging impairs immunity to promote diseases, especially respiratory viral infections. The current COVID-19 pandemic, resulting from SARS-CoV-2, induces acute pneumonia, a phenotype that is alarmingly increased with aging. In this article, we review findings of how aging alters immunity to respiratory viral infections to identify age-impacted pathways common to several viral pathogens, permitting us to speculate about potential mechanisms of age-enhanced mortality to COVID-19. Aging generally leads to exaggerated innate immunity, particularly in the form of elevated neutrophil accumulation across murine and...
Source: Journal of Immunology - June 3, 2020 Category: Allergy & Immunology Authors: Chen J, Kelley WJ, Goldstein DR Tags: J Immunol Source Type: research

Placental Myeloid Cells Protect against Zika Virus Vertical Transmission in a Rag1-Deficient Mouse Model.
Abstract The ability of Zika virus (ZIKV) to cross the placenta and infect the fetus is a key mechanism by which ZIKV causes microcephaly. How the virus crosses the placenta and the role of the immune response in this process remain unclear. In the current study, we examined how ZIKV infection affected innate immune cells within the placenta and fetus and whether these cells influenced virus vertical transmission (VTx). We found myeloid cells were elevated in the placenta of pregnant ZIKV-infected Rag1-/- mice treated with an anti-IFNAR Ab, primarily at the end of pregnancy as well as transiently in the fetus seve...
Source: Journal of Immunology - June 3, 2020 Category: Allergy & Immunology Authors: Winkler CW, Evans AB, Carmody AB, Peterson KE Tags: J Immunol Source Type: research

Inflammasomes and Pyroptosis as Therapeutic Targets for COVID-19.
Abstract The inflammatory response to severe acute respiratory syndrome-related coronavirus 2 infection has a direct impact on the clinical outcomes of coronavirus disease 2019 patients. Of the many innate immune pathways that are engaged by severe acute respiratory syndrome-related coronavirus 2, we highlight the importance of the inflammasome pathway. We discuss available pharmaceutical agents that target a critical component of inflammasome activation, signaling leading to cellular pyroptosis, and the downstream cytokines as a promising target for the treatment of severe coronavirus disease 2019-associated dise...
Source: Journal of Immunology - June 3, 2020 Category: Allergy & Immunology Authors: Yap JKY, Moriyama M, Iwasaki A Tags: J Immunol Source Type: research

Activation of the Tec Kinase ITK Controls Graded IRF4 Expression in Response to Variations in TCR Signal Strength.
In this study, we show that Ag potency regulates the kinetics but not the magnitude of NFAT1 activation in single mouse CD8+ T cells. Consequently, T cells that transduce weaker TCR signals exhibit a marked delay in Irf4 mRNA induction, resulting in decreased overall IRF4 expression in individual cells and increased heterogeneity within the clonal population. We further show that the activity of the tyrosine kinase ITK acts as a signaling catalyst that accelerates the rate of the cellular response to TCR stimulation, controlling the time to onset of Irf4 gene transcription. These findings provide insight into the function ...
Source: Journal of Immunology - June 3, 2020 Category: Allergy & Immunology Authors: Conley JM, Gallagher MP, Rao A, Berg LJ Tags: J Immunol Source Type: research

Correction: Hepatitis B Virus Surface Antigen Enhances the Sensitivity of Hepatocytes to Fas-Mediated Apoptosis via Suppression of AKT Phosphorylation.
PMID: 32482709 [PubMed - as supplied by publisher] (Source: Journal of Immunology)
Source: Journal of Immunology - June 1, 2020 Category: Allergy & Immunology Authors: Jing ZT, Liu W, Wu SX, He Y, Lin YT, Chen WN, Lin XJ, Lin X Tags: J Immunol Source Type: research

IgA Nephropathy Benefits from Compound K Treatment by Inhibiting NF- κB/NLRP3 Inflammasome and Enhancing Autophagy and SIRT1.
IgA Nephropathy Benefits from Compound K Treatment by Inhibiting NF-κB/NLRP3 Inflammasome and Enhancing Autophagy and SIRT1. J Immunol. 2020 Jun 01;: Authors: Wu CY, Hua KF, Hsu WH, Suzuki Y, Chu LJ, Lee YC, Takahata A, Lee SL, Wu CC, Nikolic-Paterson DJ, Ka SM, Chen A Abstract IgA nephropathy (IgAN), the most common primary glomerular disorder, has a relatively poor prognosis yet lacks a pathogenesis-based treatment. Compound K (CK) is a major absorbable intestinal bacterial metabolite of ginsenosides, which are bioactive components of ginseng. The present study revealed promising therapeutic e...
Source: Journal of Immunology - June 1, 2020 Category: Allergy & Immunology Authors: Wu CY, Hua KF, Hsu WH, Suzuki Y, Chu LJ, Lee YC, Takahata A, Lee SL, Wu CC, Nikolic-Paterson DJ, Ka SM, Chen A Tags: J Immunol Source Type: research

HLA Class II Specificity Assessed by High-Density Peptide Microarray Interactions.
In this study, we have used rHLA-DRB1*01:01 and HLA-DRB1*03:01 molecules to interrogate high-density peptide arrays, in casu containing 70,000 random peptides in triplicates. We demonstrate that the binding data acquired contains systematic and interpretable information reflecting the specificity of the HLA-DR molecules investigated, suitable of training predictors able to predict T cell epitopes and peptides eluted from human EBV-transformed B cells. Collectively, with a cost per peptide reduced to a few cents, combined with the flexibility of rHLA technology, this poses an attractive strategy to generate vast bodies of M...
Source: Journal of Immunology - June 1, 2020 Category: Allergy & Immunology Authors: Osterbye T, Nielsen M, Dudek NL, Ramarathinam SH, Purcell AW, Schafer-Nielsen C, Buus S Tags: J Immunol Source Type: research

Association between Subcutaneous Adipose Tissue Inflammation, Insulin Resistance, and Calorie Restriction in Obese Females.
anger J Abstract The worldwide epidemic of overweight and obesity has led to an increase in associated metabolic comorbidities. Obesity induces chronic low-grade inflammation in white adipose tissue (WAT). However, the function and regulation of both innate and adaptive immune cells in human WAT under conditions of obesity and calorie restriction (CR) is not fully understood yet. Using a randomized interventional design, we investigated postmenopausal overweight or obese female subjects who either underwent CR for 3 mo followed by a 4-wk phase of weight maintenance or had to maintain a stable weight over the whole...
Source: Journal of Immunology - June 1, 2020 Category: Allergy & Immunology Authors: Sbierski-Kind J, Mai K, Kath J, Jurisch A, Streitz M, Kuchenbecker L, Babel N, Nienen M, Jürchott K, Spranger L, Jumpertz von Schwartzenberg R, Decker AM, Krüger U, Volk HD, Spranger J Tags: J Immunol Source Type: research

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Authors: PMID: 32423923 [PubMed - in process] (Source: Journal of Immunology)
Source: Journal of Immunology - May 21, 2020 Category: Allergy & Immunology Tags: J Immunol Source Type: research

A Central Role for Ly49 Receptors in NK Cell Memory.
Abstract In the past decade, the study of NK cells was transformed by the discovery of three ways these "innate" immune cells display adaptive immune behavior, including the ability to form long-lasting, Ag-specific memories of a wide variety of immunogens. In this review, we examine these types of NK cell memory, highlighting their unique features and underlying similarities. We explore those similarities in depth, focusing on the role that Ly49 receptors play in various types of NK cell memory. From this Ly49 dependency, we will build a model by which we understand the three types of NK cell memory as ...
Source: Journal of Immunology - May 21, 2020 Category: Allergy & Immunology Authors: Wight A, Parsons BD, Rahim MMA, Makrigiannis AP Tags: J Immunol Source Type: research

COVID-19 as an Acute Inflammatory Disease.
Abstract The 2019 coronavirus disease (COVID-19) pandemic caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has created an unprecedented global crisis for the infrastructure sectors, including economic, political, healthcare, education, and research systems. Although over 90% of infected individuals are asymptomatic or manifest noncritical symptoms and will recover from the infection, those individuals presenting with critical symptoms are in urgent need of effective treatment options. Emerging data related to mechanism of severity and potential therapies for patients presenting with...
Source: Journal of Immunology - May 18, 2020 Category: Allergy & Immunology Authors: Manjili RH, Zarei M, Habibi M, Manjili MH Tags: J Immunol Source Type: research

Direct Antiviral Activity of IFN-Stimulated Genes Is Responsible for Resistance to Paramyxoviruses in ISG15-Deficient Cells.
Abstract IFNs, produced during viral infections, induce the expression of hundreds of IFN-stimulated genes (ISGs). Some ISGs have specific antiviral activity, whereas others regulate the cellular response. Besides functioning as an antiviral effector, ISG15 is a negative regulator of IFN signaling, and inherited ISG15 deficiency leads to autoinflammatory IFNopathies, in which individuals exhibit elevated ISG expression in the absence of pathogenic infection. We have recapitulated these effects in cultured human A549-ISG15-/- cells and (using A549-UBA7-/- cells) confirmed that posttranslational modification by ISG1...
Source: Journal of Immunology - May 18, 2020 Category: Allergy & Immunology Authors: Holthaus D, Vasou A, Bamford CGG, Andrejeva J, Paulus C, Randall RE, McLauchlan J, Hughes DJ Tags: J Immunol Source Type: research

Loss of Phosphatidylinositol 3-Kinase Activity in Regulatory T Cells Leads to Neuronal Inflammation.
In this study, we show that PI3Kδ is required to maintain normal Treg cell development and phenotype under homeostatic conditions but that loss of PI3Kδ alone in Treg cells does not lead to autoimmunity. However, combined loss of PI3Kα and PI3Kδ signaling resulted in increased experimental autoimmune encephalitis disease severity. Moreover, mice lacking PI3Kα and PI3Kδ in Treg cells developed spontaneous peripheral nerve inflammation. These results show a key role for PI3K signaling in Treg cell-mediated protection against CNS inflammation. PMID: 32414808 [PubMed - as supplied by pu...
Source: Journal of Immunology - May 15, 2020 Category: Allergy & Immunology Authors: Stark AK, Davenport ECM, Patton DT, Scudamore CL, Vanhaesebroeck B, Veldhoen M, Garden OA, Okkenhaug K Tags: J Immunol Source Type: research

Tracing Self-Reactive B Cells in Normal Mice.
Abstract BCR transgenic mice dominate studies of B cell tolerance; consequently, tolerance in normal mice expressing diverse sets of autoreactive B cells is poorly characterized. We have used single B cell cultures to trace self-reactivity in BCR repertoires across the first and second tolerance checkpoints and in tolerized B cell compartments of normal mice. This approach reveals affinity "setpoints" that define each checkpoint and a subset of tolerized, autoreactive B cells that is long-lived. In normal mice, the numbers of B cells avidly specific for DNA fall significantly as small pre-B become immatu...
Source: Journal of Immunology - May 15, 2020 Category: Allergy & Immunology Authors: Nojima T, Reynolds AE, Kitamura D, Kelsoe G, Kuraoka M Tags: J Immunol Source Type: research

Inhibition of Glycolysis in Pathogenic TH17 Cells through Targeting a miR -21-Peli1-c-Rel Pathway Prevents Autoimmunity.
In this study, we show that CNS-infiltrated pathogenic TH17 cells from diseased mice specifically upregulate glycolytic pathway genes compared with homeostatic intestinal TH17 cells. Bioenergetic assay and metabolomics analyses indicate that in vitro-derived pathogenic TH17 cells are highly glycolytic compared with nonpathogenic TH17 cells. Chromatin landscape analyses demonstrate TH17 cells in vivo that show distinct chromatin states, and pathogenic TH17 cells show enhanced chromatin accessibility at glycolytic genes with NF-κB binding sites. Mechanistic studies reveal that miR-21 targets the E3 ubiquitin ligase Pel...
Source: Journal of Immunology - May 15, 2020 Category: Allergy & Immunology Authors: Qiu R, Yu X, Wang L, Han Z, Yao C, Cui Y, Hou G, Dai D, Jin W, Shen N Tags: J Immunol Source Type: research

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Authors: PMID: 32366682 [PubMed - in process] (Source: Journal of Immunology)
Source: Journal of Immunology - May 7, 2020 Category: Allergy & Immunology Tags: J Immunol Source Type: research

Genome Topology Control of Antigen Receptor Gene Assembly.
Abstract The past decade has increased our understanding of how genome topology controls RAG endonuclease-mediated assembly of lymphocyte AgR genes. New technologies have illuminated how the large IgH, Igκ, TCRα/δ, and TCRβ loci fold into compact structures that place their numerous V gene segments in similar three-dimensional proximity to their distal recombination center composed of RAG-bound (D)J gene segments. Many studies have shown that CTCF and cohesin protein-mediated chromosome looping have fundamental roles in lymphocyte lineage- and developmental stage-specific locus compaction as...
Source: Journal of Immunology - May 7, 2020 Category: Allergy & Immunology Authors: Allyn BM, Lee KD, Bassing CH Tags: J Immunol Source Type: research

GPA33: A Marker to Identify Stable Human Regulatory T Cells.
Abstract FOXP3-expressing regulatory T (Treg) cells safeguard immunological tolerance. Treg cells can be generated during thymic development (called thymic Treg [tTreg] cells) or derived from mature conventional CD4+ T cells that underwent TGF-β-mediated conversion in the periphery (called peripheral Treg [pTreg] cells). Murine studies have shown that tTreg cells exhibit strong lineage fidelity, whereas pTreg cells can revert into conventional CD4+ T cells. Their stronger lineage commitment makes tTreg cells the safest cells to use in adoptive cell therapy, increasingly used to treat autoimmune and inflammato...
Source: Journal of Immunology - May 4, 2020 Category: Allergy & Immunology Authors: Opstelten R, de Kivit S, Slot MC, van den Biggelaar M, Iwaszkiewicz-Grześ D, Gliwiński M, Scott AM, Blom B, Trzonkowski P, Borst J, Cuadrado E, Amsen D Tags: J Immunol Source Type: research

Group 2 Innate Lymphoid Cells Promote Development of T Follicular Helper Cells and Initiate Allergic Sensitization to Peanuts.
Abstract Peanut allergy is a growing public concern; however, little is known about the immunological mechanism(s) that initiate the disease process. Our knowledge is also limited regarding the role of group 2 innate lymphoid cells (ILC2s) in regulating humoral immunity. To fill these major gaps in our knowledge, we investigated the immunological mechanisms involved in peanut allergen sensitization by using mouse models. To mimic environmental exposure in humans, naive BALB/c mice were exposed to peanut flour by inhalation without any exogenous adjuvants. When exposed to peanut flour, naive mice developed T follic...
Source: Journal of Immunology - May 4, 2020 Category: Allergy & Immunology Authors: Krempski JW, Kobayashi T, Iijima K, McKenzie AN, Kita H Tags: J Immunol Source Type: research

Extracellular ATP Augments Antigen-Induced Murine Mast Cell Degranulation and Allergic Responses via P2X4 Receptor Activation.
In this study, we investigated the role of P2X4 receptor in MC degranulation induced by stimulation of IgE-FcεRI complex with Ag, using bone marrow-derived MCs (BMMCs) prepared from wild type and P2X4 receptor-deficient (P2rx4-/- ) mice. ATP significantly increased Ag-induced degranulation in BMMCs prepared from wild type mice. This effect of ATP was reduced in BMMCs prepared from P2rx4-/- mice. The potentiating effect of ATP was restored by expressing P2X4 receptor in P2rx4-/- BMMCs. The P2X4 receptor-mediated effects were maintained even after differentiating into the connective tissue-type MCs. P2X4 receptor sti...
Source: Journal of Immunology - May 1, 2020 Category: Allergy & Immunology Authors: Yoshida K, Ito MA, Sato N, Obayashi K, Yamamoto K, Koizumi S, Tanaka S, Furuta K, Matsuoka I Tags: J Immunol Source Type: research

Suppression of Mll1-Complex by Stat3/Cebp β-Induced miR-21a/21b/181b Maintains the Accumulation, Homeostasis, and Immunosuppressive Function of Polymorphonuclear Myeloid-Derived Suppressor Cells.
In this study, microarray analysis revealed that the core components of the Mll1-complex, Wdr5, Ash2l, and Mll1, were concurrently downregulated by tumor-secreted factors as well as GM-CSF + IL-6 during the accumulation and activation of murine myeloid-derived suppressor cells (MDSCs). These changes were further validated by quantitative RT-PCR and Western blotting both in vitro and in vivo. The expression levels of WDR5 and ASH2L were also significantly decreased in bone marrow MDSCs of lung cancer patients compared with that of healthy controls. Functionally, ectopic expression of Wdr5, Ash2l, and Mll1 (C terminus) rever...
Source: Journal of Immunology - May 1, 2020 Category: Allergy & Immunology Authors: Zhang Z, Huang X, Wang E, Huang Y, Yang R Tags: J Immunol Source Type: research