It's time to think about circadian rhythms.
Abstract We here introduce a Review Series focussing on the important influences circadian rhythms have on immune responses. The three reviews in this series, expertly curated by Rachel Edgar, discuss how the cyclic oscillations in our cellular clock affect the innate and adaptive immune response, and how interactions with the intestinal microbiota, themselves subject to daily oscillations, also influence immune responses. As we understand more about these mechanisms, by which chronobiology contributes to immunology, it is becoming increasingly clear that they have important functions in maintaining health, influe...
Source: Immunology - November 28, 2020 Category: Allergy & Immunology Authors: Milling S Tags: Immunology Source Type: research

Recent Developments in Immunotherapy of Cancers Caused by Human Papillomaviruses.
Abstract A subset of oncogenic human papilloma viruses (HPVs) is the main cause of genital cancers, most importantly cervical cancer, as well as an increasing number of head and neck cancers. Despite the availability of prophylactic vaccines against the most prevalent oncogenic HPV types, HPV-induced malignancies are still a major health and economic burden. Besides conventional treatment with surgery, chemotherapy and radiation, immunotherapy is emerging as an efficient adjuvant option. Here we review relevant studies and ongoing clinical trials using immune checkpoint inhibitors, therapeutic vaccines, gene editi...
Source: Immunology - November 18, 2020 Category: Allergy & Immunology Authors: Fakhr E, Modic Ž, Cid Arregui A Tags: Immunology Source Type: research

Metabolic mediators: How immunometabolism directs the immune response to infection.
Abstract Here we announce the first part of an exciting new series of reviews exploring the impact of immunometabolism in the interaction between host and pathogen, and in the outcome of infection. This collection discusses the links between metabolism and epigenetic control of cell function, post-translation modifications of host proteins that determine protein fate and host cell function, the metabolic determinants of cell migration and immune cell activity, and the tussle for iron as a metabolic mediator of host-pathogen domination. Together these reviews provide engaging new insight into the metabolic signals ...
Source: Immunology - October 22, 2020 Category: Allergy & Immunology Authors: Amiel E, Perona-Wright G Tags: Immunology Source Type: research

Comparison of HLA ligand elution data and binding predictions reveals varying prediction performance for the multiple motifs recognized by HLA-DQ2.5.
In this study, we assessed how efficiently MHC class II binding predictions can identify naturally eluted peptides, and investigated instances with discrepancies between the two methods in detail. We found that, in general, MHC class II eluted ligands are predicted to bind to their reported restriction element with high affinity. But, for several studies reporting an increased number of ligands that were not predicted to bind, we found that the reported MHC restriction was ambiguous. Additional analyses determined that most of the ligands predicted to not bind, are predicted to bind other co-expressed MHC class II molecule...
Source: Immunology - October 16, 2020 Category: Allergy & Immunology Authors: Koşaloğlu-Yalçın Z, Sidney J, Chronister W, Peters B, Sette A Tags: Immunology Source Type: research

Cytokine regulated Th17 plasticity in human health and diseases.
Abstract Upon activation, naïve CD4+ T-helper (Th) cells differentiate into distinct Th effector cell lineages depending on the local cytokine environment. However, these polarized Th cells can also adapt their function and phenotype depending on the changing cytokine environment, demonstrating functional plasticity. Here, Th17 cells, which play a critical role in host protection from extracellular pathogens and in autoimmune disorders, are of particular interest. While being able to shift phenotype within their lineage, Th17 cells can also acquire characteristics of Th1, Th2, T follicular helper (Tfh) or reg...
Source: Immunology - October 16, 2020 Category: Allergy & Immunology Authors: Cerboni S, Gehrmann U, Preite S, Mitra S Tags: Immunology Source Type: research

Targeting immunometabolism in host defense against Mycobacterium tuberculosis.
Abstract In the face of ineffective vaccines, increasing antibiotic resistance, and the decline in new antibacterial drugs in the pipeline, tuberculosis (TB) still remains pandemic. Exposure to Mycobacterium tuberculosis (Mtb), which causes TB, either results in direct elimination of the pathogen, most likely by the innate immune system, or infection and containment that requires both innate and adaptive immunity to form the granuloma. Host defense strategies against infectious diseases are comprised of both host resistance, which is the ability of the host to prevent invasion or to eliminate the pathogen and dise...
Source: Immunology - October 5, 2020 Category: Allergy & Immunology Authors: Sheedy FJ, Divangahi M Tags: Immunology Source Type: research

TNFRp75 dependent immune regulation of alveolar macrophages and neutrophils during early M. tuberculosis and M. bovis BCG infection.
obs M Abstract TNF signalling through TNFRp55 and TNFRp75, and receptor shedding is important for immune activation and regulation. TNFRp75 deficiency leads to improved control of Mycobacterium tuberculosis (M. tuberculosis) infection but the effects of early innate immune events in this process are unclear. We investigated the role of TNFRp75 on cell activation and apoptosis of alveolar macrophages and neutrophils during M. tuberculosis and M. bovis BCG infection. We found increased microbicidal activity against M. tuberculosis occurred independently of IFNy and NO generation, and displayed an inverse correlation...
Source: Immunology - October 5, 2020 Category: Allergy & Immunology Authors: Walters A, Keeton R, Labuschagné A, Hsu NJ, Jacobs M Tags: Immunology Source Type: research

Improved prediction of HLA antigen presentation hotspots: applications for immunogenicity risk assessment of therapeutic proteins.
Abstract Immunogenicity risk assessment is a critical element in protein drug development. Currently, the risk assessment is most often performed using MHC-Associated Peptide Proteomics (MAPPs) and/or T cell activation assays. However, this is a highly costly procedure that encompasses limited sensitivity imposed by sample sizes, the MHC repertoire of the tested donor cohort, and the experimental procedures applied. Recent work has suggested that these techniques could be complemented by accurate, high-throughput, and cost-effective prediction in silico models. However, this work covered a very limited set of ther...
Source: Immunology - October 2, 2020 Category: Allergy & Immunology Authors: Attermann AS, Barra C, Reynisson B, Schultz HS, Leurs U, Lamberth K, Nielsen M Tags: Immunology Source Type: research

A splice acceptor variant in HLA-DRA affects the conformation and cellular localization of the class II DR alpha-chain.
Abstract Class II human leukocyte antigen (HLA) proteins are involved in the immune response by presenting pathogen-derived peptides to CD4+ T lymphocytes. At the molecular level, they are constituted by α/β heterodimers on the surface of professional antigen-presenting cells (APCs). Here, we report that the acceptor variant (rs8084) in the HLA-DRA gene mediates the transcription of an alternative version of the α-chain lacking 25 amino acids in its extracellular domain. Molecular dynamics (MD) simulations suggest this isoform undergoes structural refolding which in turn affects its stability and ...
Source: Immunology - September 27, 2020 Category: Allergy & Immunology Authors: Didonna A, Damotte V, Shams H, Matsunaga A, Caillier SJ, Dandekar R, Misra MK, Mofrad MRK, Oksenberg JR, Hollenbach JA Tags: Immunology Source Type: research

Preclinical models for studying immune responses to traumatic injury.
Abstract Traumatic injury initiates a large and complex immune response in the minutes after the initial insult, comprising of simultaneous pro- and anti-inflammatory responses. In patients that survive the initial injury, these immune responses are believed to contribute towards complications such as the development of sepsis and multiple organ dysfunction syndrome. These post-traumatic complications affect a significant proportion of patients, and are a major contributing factor for poor outcomes and an increased burden on healthcare systems. Therefore, understanding the immune responses to trauma is crucial for...
Source: Immunology - September 27, 2020 Category: Allergy & Immunology Authors: Skelton JK, Purcell R Tags: Immunology Source Type: research

Differential immune responses of immunoglobulin Z subclass members in antibacterial immunity in a zebrafish model.
Abstract Immunoglobulin Z (IgZ) or its equivalent immunoglobulin T (IgT) is a newly identified immunoglobulin (Ig) class from teleost fish. This Ig class is characterized by its involvement in mucosa-associated lymphoid tissues (MALTs) for mucosal defense against pathogen infection. Recently, several subclass members of IgZ/IgT, such as IgZ, IgZ2, Igτ1, Igτ2, and Igτ3 have been further identified from zebrafish, common carp and rainbow trout. However, the functional diversity and correlation among these subclasses remain uncertain. Here, we explored the differential immune reactions of the IgZ and IgZ2...
Source: Immunology - September 25, 2020 Category: Allergy & Immunology Authors: Ji JF, Hu CB, Shao T, Fan DD, Zhang N, Lin AF, Xiang LX, Shao JZ Tags: Immunology Source Type: research

Why do Intestinal Epithelial Cells Express MHC Class II?
Abstract Intestinal epithelial cells (IECs) constitute the border between the vast antigen load present in the intestinal lumen and the mucosal immune compartment. Their ability to express antigen processing and presentation machinery evokes the question whether IECs function as non-conventional antigen presenting cells. Major histocompatibility complex (MHC) class II expression by non-haematopoietic cells, such as IECs, is tightly regulated by the class II transactivator (CIITA) and is classically induced by IFN-γ. As MHC class II expression by IECs is upregulated under inflammatory conditions, it has been ...
Source: Immunology - September 22, 2020 Category: Allergy & Immunology Authors: Heuberger C, Pott J, Joseph Maloy K Tags: Immunology Source Type: research

Friend or Foe of Innate Lymphoid Cells in Inflammation-associated Cardiovascular Disease.
Abstract As a distinctive population of leukocytes, innate lymphoid cells (ILCs) participate in immune-mediated diseases and play crucial roles in tissue remodeling after injury. ILC lineages can divide into helper ILCs and cytotoxic ILCs. Most helper ILCs are integrated into the fabric of tissues and produce different types of cytokines involving in the pathogenesis of many kinds of cardiovascular disease and form intricate response circuits with adaptive immune cells. However, the specific phenotype and function of helper ILC subsets in cardiovascular diseases, are still poorly understood. In this review, we fir...
Source: Immunology - September 22, 2020 Category: Allergy & Immunology Authors: Gong X, Xia L, Su Z Tags: Immunology Source Type: research

Adhesion molecule crosslinking and cytokine exposure modulate IgE and non-IgE- dependent basophil activation.
Abstract Basophils are known for their role in allergic inflammation which makes them suitable targets in allergy diagnostics such as the basophil activation test (BAT) and the microfluidic immunoaffinity basophil activation test (miBAT). Beside their role in allergy, basophils have an immune modulatory role in both innate and adaptive immunity. To accomplish this mission, basophils depend on the capability to migrate from blood to extravascular tissues which includes interactions with endothelial cells, extracellular matrix, and soluble mediators. Their receptor repertoire is well known, but less is known how the...
Source: Immunology - September 20, 2020 Category: Allergy & Immunology Authors: Kalm F, Mansouri L, Russom A, Lundahl J, Nopp A Tags: Immunology Source Type: research

Inhibition of the NLRP3 inflammasome by HSP90 inhibitors.
We report that the HSP90 inhibitor EC144 effectively inhibited inflammatory processes including priming and activation of NLRP3 in vitro and in vivo. A specific inhibitor of the β HSP90 isoform was ineffective suggesting the importance of the α isoform in inflammatory signalling. EC144 inhibited IL-1β and IL-6 in vivo when administered orally, and was brain penetrant. These data suggest that HSP90 inhibitors may be useful for targeting inflammation in diverse diseases that are worsened by the presence of inflammation. PMID: 32954500 [PubMed - as supplied by publisher] (Source: Immunology)
Source: Immunology - September 19, 2020 Category: Allergy & Immunology Authors: Nizami S, Arunasalam K, Green J, Cook J, Lawrence CB, Zarganes-Tzitzikas T, Davis JB, Di Daniel E, Brough D Tags: Immunology Source Type: research

Neuroimmune Cross Talk and Evolving Pharmacotherapies in Neurodegenerative Diseases.
Abstract Neurodegeneration is characterized by gradual onset and limited availability of specific biomarkers. Apart from various aetiologies like infection, trauma, genetic mutation, etc., the interaction between the immune system and CNS is widely associated with neuronal damage in neurodegenerative diseases. The immune system plays a distinct role in disease progression and cellular homeostasis. It induces cellular as well as humoral responses, enables tissue repair, cellular healing, and clearance of cellular detritus. Aberrant and chronic activation of the immune system can damage healthy neurons. The pro-infl...
Source: Immunology - September 15, 2020 Category: Allergy & Immunology Authors: Baidya F, Bohra M, Datta A, Sarmah D, Shah B, Jagtap P, Raut S, Sarkar A, Singh U, Kalia K, Borah A, Wang X, Dave KR, Yavagal DR, Bhattacharya P Tags: Immunology Source Type: research

Interleukin-17 and ischemic stroke.
Abstract Interleukin-17 (IL-17) is a cytokine family that includes 6 members, IL-17A through IL-17F, most of them are reported to have pro-inflammatory role. Through binding to their receptors (IL-17Rs), IL-17 activates the intracellular signaling pathways to play an important role in autoimmune diseases, including rheumatoid arthritis (RA) and multiple sclerosis (MS). Ischemic stroke is a complex pathophysiological process mainly caused by regional cerebral ischemia. Inflammatory factors contribute to the physiological process of stroke that leads to poor prognosis. IL-17 plays a crucial role in promoting inflamm...
Source: Immunology - September 15, 2020 Category: Allergy & Immunology Authors: Zhang Q, Liao Y, Liu Z, Dai Y, Li Y, Li Y, Tang Y Tags: Immunology Source Type: research

Tolerance induction in memory CD4 T cells is partial and reversible.
Abstract Memory T cells respond rapidly in part because they are less reliant on heightened levels of costimulatory molecules. This enables rapid control of secondary infecting pathogens but presents challenges to efforts to control or silence memory CD4 T cells, for example in antigen specific tolerance strategies for autoimmunity. We have examined the transcriptional and functional consequences of re-activating memory CD4 T cells in the absence of an adjuvant. We find that memory CD4 T cells generated by infection or immunisation survive secondary activation with antigen delivered without adjuvant, regardless of...
Source: Immunology - September 14, 2020 Category: Allergy & Immunology Authors: Gray JI, Al-Khabouri S, Morton F, Clambey ET, Gapin L, Matsuda JL, Kappler JW, Marrack P, Garside P, Otto TD, MacLeod MK Tags: Immunology Source Type: research

Elucidating Host-Microbe Interactions in vivo by Studying Population Dynamics Using Neutral Genetic Tags.
Abstract Host-microbe interactions are highly dynamic in space and time, in particular in the case of infections. Pathogen population sizes, microbial phenotypes and the nature of the host responses often change dramatically over time. These features pose particular challenges when deciphering the underlying mechanisms of these interactions experimentally, as traditional microbiological and immunological methods mostly provide snapshots of population sizes or sparse time series. Recent approaches - combining experiments using neutral genetic tags with stochastic population dynamic models - allow a more precise qua...
Source: Immunology - September 14, 2020 Category: Allergy & Immunology Authors: Hausmann A, Hardt WD Tags: Immunology Source Type: research

T cell responses and therapies against SARS-CoV-2 infection.
Abstract Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, a novel coronavirus strain. Some studies suggest that COVID-19 could be an immune-related disease, and failure of effective immune responses in initial stages of viral infection contribute to systemic inflammation and tissue damage, leading to worse disease outcomes. T cells can act as a double-edge sword with both pro- and anti-roles in the progression of COVID-19. Thus, better understanding of their roles in immune responses to SARS-CoV-2 infection is crucial. T cells primarily react to the spike protein on the coronavirus to initiate antivira...
Source: Immunology - September 14, 2020 Category: Allergy & Immunology Authors: Toor SM, Saleh R, Sasidharan Nair V, Taha RZ, Elkord E Tags: Immunology Source Type: research

Variation in genes implicated in B-cell maturation and antibody production affects susceptibility to pemphigus.
to DG Abstract Pemphigus foliaceus (PF) is an autoimmune blistering skin disease characterized by the presence of pathogenic autoantibodies against desmoglein 1, a component of intercellular desmosome junctions. PF occurs sporadically across the globe and is endemic in some Brazilian regions. Because PF is a B-cell-mediated disease, we aimed to study the impact of variants within genes encoding molecules involved in the different steps of B-cell development and antibody production on the susceptibility of endemic PF. We analyzed 3,336 single nucleotide polymorphisms (SNPs) from 167 candidate genes genotyped with I...
Source: Immunology - September 13, 2020 Category: Allergy & Immunology Authors: Calonga-Solís V, Amorim LM, Farias TDJ, Luiza Petzl-Erler M, Malheiros D, Augusto DG Tags: Immunology Source Type: research

Implications of cellular metabolism for immune cell migration.
Abstract Cell migration is an essential, energetically-demanding process in immunity. Immune cells navigate the body via chemokines and other immune mediators, which are altered under inflammatory conditions of injury or infection. Several factors determine the migratory abilities of different types of immune cells in diverse contexts, including the precise coordination of cytoskeletal remodeling, the expression of specific chemokine receptors and integrins, and environmental conditions. In this review, we present an overview of recent advances in our understanding of the relationship of each of these factors with...
Source: Immunology - September 12, 2020 Category: Allergy & Immunology Authors: Guak H, Krawczyk CM Tags: Immunology Source Type: research

Interferon regulatory factor 4 deficiency in CD8+ T cells abrogates terminal effector differentiation and promotes transplant acceptance.
Abstract Allogeneic CD8+ cytotoxic T cells play an essential role in rejecting transplanted allografts, but how their effector function is regulated on a transcriptional level remains unclear. Herein we investigate the role of interferon regulatory factor 4 (IRF4) in controlling CD8+ T cell function in response to transplant. B6.Rag1-/- mice were adoptively transferred with CD8+ T cells isolated from either Irf4fl/fl Cd4-Cre (T cell specific Irf4-deficient) or Irf4fl/fl control mice, followed by Balb/c skin transplantation. Recipients that received Irf4-deficient CD8+ T cells permanently accepted the skin allograf...
Source: Immunology - September 5, 2020 Category: Allergy & Immunology Authors: Zou D, Fu J, Guo Z, Chen W Tags: Immunology Source Type: research

Neuromedin U: potential roles in immunity and inflammation.
Abstract Since the discovery of Neuromedin U (NmU) from porcine spinal cord in 1985, this neuropeptide has been subsequently identified in many other species with multiple physiological and pathophysiological roles detected, ranging from smooth muscle contraction, feeding, energy balance to tumorigenesis. Intriguingly, NmU is also emerging to play pro-inflammatory roles involving immune cell activation and cytokine release in a neuron-dependent or neuron-independent manner. The NmU-mediated inflammatory responses have already been observed in worm infection, sepsis, autoimmune arthritis and allergic animal models....
Source: Immunology - September 4, 2020 Category: Allergy & Immunology Authors: Ye Y, Liang Z, Xue L Tags: Immunology Source Type: research

Pre-selection TCR repertoire predicts CD4+ and CD8+ T cell differentiation state.
In conclusion, these findings provide deeper insight into the generation and evolution of TCR repertoire generation. PMID: 32875554 [PubMed - as supplied by publisher] (Source: Immunology)
Source: Immunology - September 1, 2020 Category: Allergy & Immunology Authors: Hou X, Chen W, Zhang X, Wang G, Chen J, Zeng P, Fu X, Zhang Q, Liu X, Diao H Tags: Immunology Source Type: research

The role of hydrogen sulfide signaling in macrophage activation.
Abstract Hydrogen sulfide (H2 S) is the latest identified small gaseous mediator enabled by its lipophilic nature to freely permeate the biological membranes. Initially, H2 S was recognized by its roles in neuronal activity and vascular relaxation, which makes it an important molecule involved in paracrine signaling pathways. Recently, the immune regulatory function of gasotransmitters, H2 S in particular, is increasingly being appreciated. Endogenous H2 S level has been linked to macrophage activation, polarization, and inflammasome formation. Mechanistically, H2 S-induced protein S-sulfhydration suppresses sever...
Source: Immunology - September 1, 2020 Category: Allergy & Immunology Authors: Sun F, Luo JH, Yue TT, Wang FX, Yang CL, Zhang S, Wang XQ, Wang CY Tags: Immunology Source Type: research

Quantitative and qualitative alterations of circulating myeloid cells and plasmacytoid DC in SARS-CoV-2 infection.
Abstract SARS-CoV-2 is responsible for a new infectious disease (COVID-19) in which individuals can either remain asymptomatic or progress from mild to severe clinical conditions including acute respiratory distress syndrome and multiple organ failure. The immune mechanisms that potentially orchestrate the pathology in SARS-CoV-2 infection are complex and only partially understood. There is still paucity of data on the features of myeloid cells involved in this viral infection. For this reason, we investigated the different activation status profile and the subsets distribution of myeloid cells as well as their co...
Source: Immunology - August 31, 2020 Category: Allergy & Immunology Authors: Peruzzi B, Bencini S, Capone M, Mazzoni A, Maggi L, Salvati L, Vanni A, Orazzini C, Nozzoli C, Morettini A, Poggesi L, Pieralli F, Peris A, Bartoloni A, Vannucchi AM, Liotta F, Caporale R, Cosmi L, Annunziato F Tags: Immunology Source Type: research

Authors: Abstract Retraction: Emoto, M., Shimizu, T., Koike, H., Yoshizawa, I., Hurwitz, R., Kaufmann, S.H.E. and Emoto, Y. (2010), Dissociated expression of natural killer 1.1 and T-cell receptor by invariant natural killer T cells after interleukin-12 receptor and T-cell receptor signalling. Immunology, 129: 62-74. The above article, published online on 08 December 2009 in Wiley Online Library (, has been retracted by agreement between the Editor-in-Chief of Immunology and John Wiley & Sons Ltd. The retraction has been agreed following ...
Source: Immunology - August 29, 2020 Category: Allergy & Immunology Tags: Immunology Source Type: research

Immunological partners: the gut microbiome in homeostasis and disease.
PMID: 32851647 [PubMed - in process] (Source: Immunology)
Source: Immunology - August 29, 2020 Category: Allergy & Immunology Authors: La Flamme AC, Milling S Tags: Immunology Source Type: research

Cytoskeleton Protein 4.1R Regulates B cell fate by Modulating the Canonical NF- κB Pathway.
Cytoskeleton Protein 4.1R Regulates B cell fate by Modulating the Canonical NF-κB Pathway. Immunology. 2020 Aug 27;: Authors: Liang T, Guo Y, Li M, Ding C, Sang S, Zhou T, Shao Q, Liu X, Lu J, Ji Z, Wang T, Kang Q Abstract During the immune response, B cell fate can enter the memory pathway characterized by class switch recombination (CSR) or undergo plasma cell differentiation (PCD) to secrete immunoglobulin (Ig). Both of these processes occur in activated B cells, which are reported relate to membrane-association proteins and adaptors. Protein 4.1R acts as an adaptor, linking membrane proteins...
Source: Immunology - August 26, 2020 Category: Allergy & Immunology Authors: Liang T, Guo Y, Li M, Ding C, Sang S, Zhou T, Shao Q, Liu X, Lu J, Ji Z, Wang T, Kang Q Tags: Immunology Source Type: research

MicroRNA-7 Negatively Regulates Toll-Like Receptor 4 Signaling Pathway through FAM177A.
Abstract Toll-like receptor (TLR) 4 signaling is critical for innate immunoinflammatory response and widely triggers the development of various types of clinical diseases. MicroRNA-7 (miR-7) is well documented plays an important regulator role in various biological events. However, the exact role of miR-7 in TLR4 signaling pathway remains to be fully elucidated. In present study, we found that miR-7 expression in TLR4 signaling-activated bone marrow-derived macrophages (BMDMs) stimulated by LPS dramatically increased. Importantly, miR-7 deficiency significantly enhanced the production of related inflammatory cytok...
Source: Immunology - August 26, 2020 Category: Allergy & Immunology Authors: Chen H, Guo M, Yue D, Zhao J, Zhou Y, Chen C, Liang G, Xu L Tags: Immunology Source Type: research

TLR5 activation in hepatocytes alleviates the functional suppression of intrahepatic CD8+ T cells.
Abstract The liver is an immune privileged organ with a tolerogenic environment for maintaining liver homeostasis. This hepatic tolerance limits the intrahepatic CD8+ T cell response for eliminating infections. The tolerant microenvironment in the liver is orchestrated by liver-specific immunoregulatory cells that can be functionally regulated by pathogen associated molecule patterns (PAMPs). Here, we report that flagellin, a key PAMP of gut bacteria, modulates the intrahepatic CD8+ T cell response by activating the TLR5 signaling pathway of hepatocytes. We found that mice treated with Salmonella-derived recombina...
Source: Immunology - August 26, 2020 Category: Allergy & Immunology Authors: Yan H, Zhong M, Yang J, Guo J, Yu J, Yang Y, Ma Z, Zhao B, Zhang Y, Wang J, Wu C, Dittmer U, Yang D, Lu M, Zhang E, Yan H Tags: Immunology Source Type: research

Mononuclear phagocyte regulation by the transcription factor Blimp-1 in health and disease.
Abstract Blimp-1, the transcription factor encoded by the gene Prdm1, plays a number of crucial roles in the adaptive immune system, which result in the maintenance of key effector functions of B and T cells. Emerging clinical data, as well as mechanistic evidence from mouse studies, has additionally identified critical functions of Blimp-1 in the maintenance of immune homeostasis by the mononuclear phagocyte system. Blimp-1 regulation of gene expression affects various aspects of mononuclear phagocyte biology, including developmental programs such as fate decisions of monocytes entering peripheral tissue, and fun...
Source: Immunology - August 15, 2020 Category: Allergy & Immunology Authors: Ulmert I, Henriques-Oliveira L, Pereira CF, Lahl K Tags: Immunology Source Type: research

The cytotoxic molecule granulysin is capable of inducing either chemotaxis or fugetaxis in dendritic cells depending on maturation: a role for V δ2+ γδ T cells in the modulation of immune response to tumour?
In this study, Vδ2+ γδ T cells were activated by stimulation of peripheral blood mononuclear cells (PBMC) with zoledronic acid (ZA) or Bacillus Calmette Guérin (BCG), or were isolated and cultured with tumour targets. While a large proportion of resting Vδ2+ γδ T cells expressed 15kDa granulysin, 9kDa granulysin expression was induced only after stimulation with BCG. Increased levels of activation and granulysin secretion were also observed when Vδ2+ γδ T cells were cultured with the human B cell lymphoma line Daudi. High concentrations of recombinant 15kDa granu...
Source: Immunology - August 12, 2020 Category: Allergy & Immunology Authors: Sparrow EL, Fowler DW, Fenn J, Caron J, Copier J, Dalgleish AG, Bodman-Smith MD Tags: Immunology Source Type: research

P38 MAPK Signaling Mediates Retinoic Acid-Induced CD103 Expression in Human Dendritic Cells.
In this study, we analyzed the cell type specificity and the molecular mechanisms involved in RA-induced CD103 expression. We show that RA treatment caused a significant upregulation of CD103 in differentiated monocyte-derived DCs and blood DCs, but not in differentiated monocyte-derived macrophages or T cells. DC treatment with an RARα agonist lead to a similar increase in CD103 expression as RA treatment, while RARA gene silencing with siRNA blocked RA-induced upregulation of CD103, pointing to a major role of RARα in the regulation of CD103 expression. To elucidate RA-induced signaling downstream of RAR&alph...
Source: Immunology - July 31, 2020 Category: Allergy & Immunology Authors: Roe MM, Hashimi M, Swain S, Woo KM, Bimczok D Tags: Immunology Source Type: research

The role of O-GlcNAcylation in immunity against infections.
Abstract Mounting an effective immune response is crucial for the host to protect itself against invading pathogens. It is now well appreciated that reprogramming of core metabolic pathways in immune cells is a key requirement for their activation and function during infections. The role of several ancillary metabolic pathways in shaping immune cell function is less well understood. One such pathway, for which interest has recently been growing, is the hexosamine biosynthesis pathway (HBP) that generates uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the donor substrate for a specific form of glycosylation ...
Source: Immunology - July 31, 2020 Category: Allergy & Immunology Authors: Quik M, Hokke CH, Everts B Tags: Immunology Source Type: research

Authors: PMID: 32686182 [PubMed - in process] (Source: Immunology)
Source: Immunology - July 21, 2020 Category: Allergy & Immunology Tags: Immunology Source Type: research

T cells and cytokines in inflamed psoriatic skin. Who's in charge?
Abstract Inflammation in psoriasis is driven through the IL-23/IL-17 pathway. Monoclonal antibodies targeting cytokines in the pathway have proven highly effective and are widely used in clinical practice. There is still much to learn, however, about how these pathogenic responses are controlled, particularly with respect to the highly immunologically active molecules produced by the inflamed skin tissue itself. These tissue-derived molecules, which include IL-33, play important roles in modulating chronic inflammation that we are only beginning to understand. Here we highlight new research indicating a role for I...
Source: Immunology - July 21, 2020 Category: Allergy & Immunology Authors: Milling S, Siebert S Tags: Immunology Source Type: research

Authors: PMID: 32686184 [PubMed - in process] (Source: Immunology)
Source: Immunology - July 21, 2020 Category: Allergy & Immunology Tags: Immunology Source Type: research

Viruses and asthma: the role of common respiratory viruses in asthma and its potential meaning for SARS-CoV-2.
Abstract Viral infections and atopic diseases are closely related and contribute to each other. The physiological deficiencies and immune mechanisms that underlie atopic diseases can result in a suboptimal defense against multiple viruses and promote a suitable environment for their proliferation and dissemination. Viral infections, on the other hand, can induce per se several immunological mechanisms involved in allergic inflammation capable to promote the initiation or exacerbation of atopic diseases such as atopic asthma. In a world that is affected more and more by factors that significantly impact the prevale...
Source: Immunology - July 19, 2020 Category: Allergy & Immunology Authors: Novak N, Cabanillas B Tags: Immunology Source Type: research

Quantifying immunoregulation by autoantigen-specific T-regulatory type 1 cells in mice with simultaneous hepatic and extra-hepatic autoimmune disorders.
Abstract Nanoparticles displaying autoimmune disease-relevant peptide-major histocompatibility complex class II molecules (pMHCII-NPs) trigger cognate T-regulatory type 1 (Tr1)-cell formation and expansion, capable of reversing organ-specific autoimmune responses. These pMHCII-NPs that display epitopes from mitochondrial protein can blunt the progression of both autoimmune hepatitis (AIH) and experimental autoimmune encephalomyelitis (EAE) in mice carrying either disease. However, with comorbid mice having both diseases, these pMHCII-NPs selectively treat AIH. In contrast, pMHCII-NPs displaying central nervous sys...
Source: Immunology - July 19, 2020 Category: Allergy & Immunology Authors: Jamaleddine H, Santamaria P, Khadra A Tags: Immunology Source Type: research

Targeting Metabolism to Reverse T-cell Exhaustion in Chronic Viral Infections.
Abstract CD8 T-cells are an essential component of immune response to viral infections; however, in certain instances, such as chronic infections, they can reach an exhausted state, where T-cells loose glycolytic activity together with cytotoxic capacity. Recent research has indicated that correcting this dysfunctional metabolic state could be key to reversing exhaustion and allowing for proper clearance of chronic viral infections. Here, we review current knowledge about T-cell exhaustion during infection and discuss strategies targeting metabolism that hold promise for its reversal. PMID: 32681647 [PubMed -...
Source: Immunology - July 17, 2020 Category: Allergy & Immunology Authors: Sears JD, Waldron KJ, Wei J, Chang CH Tags: Immunology Source Type: research

Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data.
Abstract According to publicly available transcriptome datasets, the abundance of Annexin A3 (ANXA3) is robustly increased during the course of sepsis; however, no studies have examined the biological significance or clinical relevance of ANXA3 in this pathology. Here we explored this interpretation gap and identified possible directions for future research. Based on reference transcriptome datasets, we found that ANXA3 expression is restricted to neutrophils, is upregulated in vitro after exposure to plasma obtained from septic patients, and is associated with adverse clinical outcomes. Secondly, an increase in A...
Source: Immunology - July 17, 2020 Category: Allergy & Immunology Authors: Toufiq M, Roelands J, Alfaki M, Ahamed Kabeer B, Saadaoui M, Prasath Lakshmanan A, Kumar Bangarusamy D, Murugesan S, Bedognetti D, Hendrickx W, Al Khodor S, Terranegra A, Rinchai D, Chaussabel D, Garand M Tags: Immunology Source Type: research

The battle for iron in enteric infections.
st JN Abstract Iron is an essential element for almost all living organisms, which can also be extremely toxic in high concentrations. All organisms must therefore employ homeostatic mechanisms to finely regulate iron uptake, usage and storage in the face of dynamic environmental conditions. The critical step in mammalian systemic iron homeostasis is the fine regulation of dietary iron absorption. However, since the gastrointestinal system is also home to>1014 bacteria, all of which engage in their own programs of iron homeostasis, the gut represents an anatomical location where the inter-kingdom fight for iron...
Source: Immunology - July 7, 2020 Category: Allergy & Immunology Authors: Sousa Gerós A, Simmons A, Drakesmith H, Aulicino A, Frost JN Tags: Immunology Source Type: research

MHC class I transactivator NLRC5 in host immunity, cancer and beyond.
Abstract The presentation of antigenic peptides by major histocompatibility complex (MHC) class I and class II molecules are crucial for activation of the adaptive immune system. The nucleotide-binding domain and leucine-rich repeat receptor family member, CIITA and NLRC5 functions as the major transcriptional activator of MHC class II and class I gene expression, respectively. Since the identification of NLRC5 as the master regulator of MHC class I and class I related genes, there has been major advances in understanding the function of NLRC5 in infectious diseases and cancer. Here, we discuss the biological sign...
Source: Immunology - July 6, 2020 Category: Allergy & Immunology Authors: Cho SX, Vijayan S, Yoo JS, Watanabe T, Ouda R, Ning A, Kobayashi KS Tags: Immunology Source Type: research

Generation of multiepitope cancer vaccines based on large combinatorial libraries of survivin-derived mutant epitopes.
kian G, Manoutcharian K Abstract Immune tolerance is the main challenge in the field of cancer vaccines, therefore, modified peptide sequences or naturally occurring mutated versions of cancer-related wild-type (WT) antigens represent a promising pathway. However, low immunogenicity of mutation-induced neoantigens and, particularly, their incapacity to activate CD8+ T cells are generating doubts on the success of neoantigen-based cancer vaccines in clinical trials. We developed a novel vaccine approach based on a new class of vaccine immunogens, called Variable Epitope Libraries (VELs). We used 3 regions of surviv...
Source: Immunology - July 2, 2020 Category: Allergy & Immunology Authors: Domínguez-Romero AN, Martínez-Cortés F, Munguía ME, Odales J, Gevorkian G, Manoutcharian K Tags: Immunology Source Type: research

Schistosome and intestinal helminth modulation of Macrophage Immunometabolism.
Abstract Macrophages are fundamental to sustain physiological equilibrium and to regulate the pathogenesis of parasitic and metabolic processes. The functional heterogeneity and immune responses of macrophages are shaped by cellular metabolism in response to the host's intrinsic factors, environmental cues and other stimuli during disease. Parasite infections induce a complex cascade of cytokines and metabolites that profoundly remodel the metabolic status of macrophages. In particular, helminths polarize macrophages to a M2 state and induce a metabolic shift towards a reliance on oxidative phosphorylation, lipid ...
Source: Immunology - July 1, 2020 Category: Allergy & Immunology Authors: Cortes-Selva D, Fairfax K Tags: Immunology Source Type: research

A behind the scenes tour of the IEDB curation process: an optimized process empirically integrating automation and human curation efforts.
Abstract The Immune Epitope Database and Analysis Resource (IEDB) provides the scientific community open access to epitope data, as well as epitope prediction and analysis tools. The IEDB houses the most extensive collection of experimentally validated B cell and T cell epitope data, sourced primarily from published literature by expert curation. The data procurement requires systematic identification, categorization, curation, and quality-checking processes. Here we provide insights into these processes, with particular focus on the dividends they have paid in terms of attaining project milestones, as well as how...
Source: Immunology - July 1, 2020 Category: Allergy & Immunology Authors: Salimi N, Edwards L, Foos G, Greenbaum JA, Martini S, Reardon B, Shackelford D, Vita R, Zalman L, Peters B, Sette A Tags: Immunology Source Type: research

Role of myeloid cells in the regulation of ILC2-mediated allergic inflammation.
Abstract Group 2 innate lymphoid cells (ILC2s) are an important component of the innate immune system that execute important effector functions at barrier surfaces, such as lung and skin. Like Th2 cells, ILC2s are able to release high amounts of type 2 cytokines that are essential in inducing allergic inflammation and eliminating helminth infections. The past few years have contributed to our better understanding of the interactions between ILC2s and other cells of immune system via soluble factors or in a cell-cell contact manner. Myeloid cells, including mononuclear leukocytes and polymorphonuclear leukocytes, a...
Source: Immunology - June 30, 2020 Category: Allergy & Immunology Authors: Lei A, He Y, Yang Q, Li X, Li R Tags: Immunology Source Type: research

Gasdermin D-independent release of interleukin-1b by living macrophages in response to mycoplasmal lipoproteins and lipopeptides.
Abstract Interleukin-1b (IL-1b) plays pivotal roles in controlling bacterial infections and is produced after the processing of pro-IL-1b by caspase-1 which is activated by the inflammasome. In addition, caspase-1 cleaves the cytosolic protein, gasdermin-D (GSDMD), whose N-terminal fragment subsequently forms a pore in the plasma membrane, leading to the pyroptic cell death-mediated release of IL-1b. Living cells can also release IL-1b via GSDMD pores or other unconventional secretory pathways. However, the precise mechanisms are poorly defined. Here, we show that lipoproteins from Mycoplasma salivarium (MsLP) and...
Source: Immunology - June 25, 2020 Category: Allergy & Immunology Authors: Saeki A, Tsuchiya K, Suda T, Into T, Hasebe A, Suzuki T, Shibata KI Tags: Immunology Source Type: research