Microbes mediate mitochondrial misinformation to misguide neutrophils.
Discussion on LPS disruption of mitochondrial localization and autocrine purinergic signaling in neutrophil chemotaxis for control of E. coli infection. PMID: 31633233 [PubMed - as supplied by publisher] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - October 21, 2019 Category: Hematology Authors: Karmakar M, Dubyak GR Tags: J Leukoc Biol Source Type: research

Anti-streptococcal antibody and T-cell interactions with vascular endothelial cells initiate the development of rheumatic carditis.
Abstract The role of group A streptococcal and Streptococcus dysgalactiae subspecies equisimilis M-protein specific Abs and T-cells in endothelial cell activation was investigated using cultured rat aortic endothelial cells, and in a rat model of autoimmune valvulitis. Heat inactivated serum and mononuclear cells from streptococcal M-protein immunized rats independently induced upregulation of the endothelial cell adhesion molecules, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in cultured cells. We also observed T-cell migration across endothelial cell monolayers incubated...
Source: Journal of Leukocyte Biology - October 16, 2019 Category: Hematology Authors: Sikder S, Rush CM, Govan BL, Alim MA, Ketheesan N Tags: J Leukoc Biol Source Type: research

Low Tregs: A targetable risk factor for life-threatening cardiovascular complications after major noncardiac surgery.
Discussion on Tregs that have anti-inflammatory and anti-atherogenic properties as an ideal therapeutic target to reduce fatal cardiovascular deaths following major noncardiac surgery. PMID: 31608500 [PubMed - as supplied by publisher] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - October 14, 2019 Category: Hematology Authors: Kyaw T, Bobik A Tags: J Leukoc Biol Source Type: research

Inflammasomes in the pathophysiology of autoinflammatory syndromes.
Abstract Inflammasomes are a specialized group of intracellular sensors that are key components of the host innate immune system. Autoinflammatory diseases are disorders of the innate immune system that are characterized by recurrent inflammation and serious complications. Dysregulation of the inflammasome is associated with the onset and progression of several autoinflammatory and autoimmune diseases, including cryopyrin-associated periodic fever syndrome, familial Mediterranean fever, rheumatoid arthritis, and systemic lupus erythematosus. In this review, we discuss the involvement of various inflammasome compon...
Source: Journal of Leukocyte Biology - October 14, 2019 Category: Hematology Authors: Tartey S, Kanneganti TD Tags: J Leukoc Biol Source Type: research

Up-regulation of miR-27a promotes monocyte-mediated inflammatory responses in Kawasaki disease by inhibiting function of B10 cells.
Abstract Kawasaki disease (KD) is an acute systemic vasculitis and activation of monocytes plays a central role in the pathogenesis of it. B10 cells, a B cell subset with negative regulatory properties, are functionally identified by their ability to express cytoplasmic IL-10 after ex vivo stimulation. Here, we aimed to explore the functional role of B10 cells during monocyte-mediated inflammatory responses in KD, as well as elucidate the underlying microRNA (miRNA)-mediated regulatory mechanisms. Expression of IL-10 by each group of B cells (total B cells, transitional B cells, naïve B cells, and memory B ce...
Source: Journal of Leukocyte Biology - October 3, 2019 Category: Hematology Authors: Luo Y, Yang J, Zhang C, Jin Y, Pan H, Liu L, Gong Y, Xia Y, Wang G, Zhang J, Li C, Li Q Tags: J Leukoc Biol Source Type: research

Age-related alterations in human gut CD4 T cell phenotype, T helper cell frequencies, and functional responses to enteric bacteria.
In this study, we evaluated the direct ex vivo frequency, activation/inhibitory phenotype, death profiles, and in vitro functional responses of human jejunum LP CD4 T cells, including Th1, Th17, and Th22 subsets isolated from younger (65years) persons. Expression of the co-inhibitory molecule CTLA-4 was significantly lower in older CD4 T cells, whereas expression of HLA-DR, CD38, CD57, and PD-1 were not significantly different between groups. Total CD4 T cell frequencies were similar between age groups, but lower frequencies and numbers of Th17 cells were observed directly ex vivo in older samples. Older Th17 and Th1 cells...
Source: Journal of Leukocyte Biology - October 1, 2019 Category: Hematology Authors: Dillon SM, Liu J, Purba CM, Christians AJ, Kibbie JJ, Castleman MJ, McCarter MD, Wilson CC Tags: J Leukoc Biol Source Type: research

β-Catenin stabilization in NOD dendritic cells increases IL-12 production and subsequent induction of IFN-γ-producing T cells.
In this study, we report that β-catenin, a multifunctional protein involved in inflammation, is dramatically increased in DC from NOD mice. We further investigated the mechanisms leading to accumulation of β-catenin in NOD DC and its role in the inflammatory pathogenic responses associated with T1D. Hyperphosphorylation of β-catenin at a stabilizing residue, serine 552, mediated by activation of Akt, appears to lead to β-catenin accumulation in NOD DC. Elevated β-catenin in DC correlated with IL-12 production and induction of IFN-γ-producing CD4 cells. On the one hand, knockdown/inhibition of...
Source: Journal of Leukocyte Biology - September 30, 2019 Category: Hematology Authors: Zirnheld AL, Villard M, Harrison AM, Kosiewicz MM, Alard P Tags: J Leukoc Biol Source Type: research

Knowledge is power-Rational design of cancer immunotherapy.
Discussion on how our increasing knowledge on tumor immunity and host defense mechanisms has drastically changed our ability to improve cancer outcomes through the rational design of immunotherapies. PMID: 31556463 [PubMed - as supplied by publisher] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - September 26, 2019 Category: Hematology Authors: De Paris K Tags: J Leukoc Biol Source Type: research

Human leukocytes differentially express endocannabinoid-glycerol lipases and hydrolyze 2-arachidonoyl-glycerol and its metabolites from the 15-lipoxygenase and cyclooxygenase pathways.
, Flamand N Abstract 2-Arachidonoyl-glycerol (2-AG) is an endocannabinoid with anti-inflammatory properties. Blocking 2-AG hydrolysis to enhance CB2 signaling has proven effective in mouse models of inflammation. However, the expression of 2-AG lipases has never been thoroughly investigated in human leukocytes. Herein, we investigated the expression of seven 2-AG hydrolases by human blood leukocytes and alveolar macrophages (AMs) and found the following protein expression pattern: monoacylglycerol (MAG lipase; eosinophils, AMs, monocytes), carboxylesterase (CES1; monocytes, AMs), palmitoyl-protein thioesterase (PP...
Source: Journal of Leukocyte Biology - September 26, 2019 Category: Hematology Authors: Turcotte C, Dumais É, Archambault AS, Martin C, Blanchet MR, Bissonnette É, Boulet LP, Laviolette M, Marzo VD, Flamand N Tags: J Leukoc Biol Source Type: research

Decoding communication patterns of the innate immune system by quantitative proteomics.
Abstract The innate immune system is a collective network of cell types involved in cell recruitment and activation using a robust and refined communication system. Engagement of receptor-mediated intracellular signaling initiates communication cascades by conveying information about the host cell status to surrounding cells for surveillance and protection. Comprehensive profiling of innate immune cells is challenging due to low cell numbers, high dynamic range of the cellular proteome, low abundance of secreted proteins, and the release of degradative enzymes (e.g., proteases). However, recent advances in mass sp...
Source: Journal of Leukocyte Biology - September 26, 2019 Category: Hematology Authors: Sukumaran A, Coish JM, Yeung J, Muselius B, Gadjeva M, MacNeil AJ, Geddes-McAlister J Tags: J Leukoc Biol Source Type: research

Colony-stimulating factor-1- and interleukin-34-derived macrophages differ in their susceptibility to Mycobacterium marinum.
Abstract Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains the leading global cause of death from an infectious agent. Mycobacteria thrive within their host Mϕs and presently, there is no animal model that permits combined in vitro and in vivo study of mycobacteria-host Mϕ interactions. Mycobacterium marinum (Mm), which causes TB in aquatic vertebrates, has become a promising model for TB research, owing to its close genetic relatedness to Mtb and the availability of alternative, natural host aquatic animal models. Here, we adopted the Xenopus laevis frog-Mm surrogate infection ...
Source: Journal of Leukocyte Biology - September 19, 2019 Category: Hematology Authors: Popovic M, Yaparla A, Paquin-Proulx D, Koubourli DV, Webb R, Firmani M, Grayfer L Tags: J Leukoc Biol Source Type: research

Frontline Science: Antagonism between regular and atypical Cxcr3 receptors regulates macrophage migration during infection and injury in zebrafish.
In this study, we generated a cxcr3.3 CRISPR-mutant to functionally dissect the antagonistic interplay among the cxcr3 paralogs in the immune response. We observed that cxcr3.3 mutants are more susceptible to mycobacterial infection, whereas cxcr3.2 mutants are more resistant. Furthermore, macrophages in the cxcr3.3 mutant are more motile, show higher activation status, and are recruited more efficiently to sites of infection or injury. Our results suggest that Cxcr3.3 is an ACKR that regulates the activity of Cxcr3.2 by scavenging common ligands and that silencing the scavenging function of Cxcr3.3 results in an exacerbat...
Source: Journal of Leukocyte Biology - September 17, 2019 Category: Hematology Authors: Sommer F, Torraca V, Kamel SM, Lombardi A, Meijer AH Tags: J Leukoc Biol Source Type: research

TLRs toll for Tregs.
Discussion on TLR3 triggering in CD4 T cells induces IFN beta and IL10-producing iTregs that suppress food allergy. PMID: 31529712 [PubMed - as supplied by publisher] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - September 17, 2019 Category: Hematology Authors: Aksoy E Tags: J Leukoc Biol Source Type: research

Frontline Science: Low regulatory T cells predict perioperative major adverse cardiovascular and cerebrovascular events after noncardiac surgery.
Abstract Immune cells drive atherosclerotic lesion progression and plaque destabilization. Coronary heart disease patients undergoing noncardiac surgery are at risk for perioperative major adverse cardiac and cerebrovascular events (MACCE). It is unclear whether differential leukocyte subpopulations contribute to perioperative MACCE and thereby could aid identification of patients prone to perioperative cardiovascular events. First, we performed a hypothesis-generating post hoc analysis of the LeukoCAPE-1 study (n = 38). We analyzed preoperative counts of 6 leukocyte subpopulations in coronary heart dise...
Source: Journal of Leukocyte Biology - September 15, 2019 Category: Hematology Authors: Scholz AS, Handke J, Gillmann HJ, Zhang Q, Dehne S, Janssen H, Arens C, Espeter F, Sander A, Giannitsis E, Uhle F, Weigand MA, Motsch J, Larmann J Tags: J Leukoc Biol Source Type: research

Syk-dependent glycolytic reprogramming in dendritic cells regulates IL-1 β production to β-glucan ligands in a TLR-independent manner.
Syk-dependent glycolytic reprogramming in dendritic cells regulates IL-1β production to β-glucan ligands in a TLR-independent manner. J Leukoc Biol. 2019 Sep 11;: Authors: Thwe PM, Fritz DI, Snyder JP, Smith PR, Curtis KD, O'Donnell A, Galasso NA, Sepaniac LA, Adamik BJ, Hoyt LR, Rodriguez PD, Hogan TC, Schmidt AF, Poynter ME, Amiel E Abstract Dendritic cells (DCs) activated via TLR ligation experience metabolic reprogramming, in which the cells are heavily dependent on glucose and glycolysis for the synthesis of molecular building blocks essential for maturation, cytokine production, and th...
Source: Journal of Leukocyte Biology - September 11, 2019 Category: Hematology Authors: Thwe PM, Fritz DI, Snyder JP, Smith PR, Curtis KD, O'Donnell A, Galasso NA, Sepaniac LA, Adamik BJ, Hoyt LR, Rodriguez PD, Hogan TC, Schmidt AF, Poynter ME, Amiel E Tags: J Leukoc Biol Source Type: research

RNF144B inhibits LPS-induced inflammatory responses via binding TBK1.
Abstract Innate immune responses need to be precisely controlled to avoid prolonged inflammation and prevent unwanted damage to the host. Here, we report that RNF144B responded dynamically to LPS stimulation and negatively regulated LPS-induced inflammation. We found that RNF144B interacted with the scaffold/dimerization domain (SDD) of TANK binding kinase 1 (TBK1) through the in between RING (IBR) domain to inhibit its phosphorylation and K63-linked polyubiquitination, which led to TBK1 inactivation, IRF3 dephosphorylation, and IFN-β reduction. RNF144B knockdown with siRNA increased IRF3 activation and IFN-&...
Source: Journal of Leukocyte Biology - September 11, 2019 Category: Hematology Authors: Zhang Z, Zhang L, Wang B, Zhu X, Zhao L, Chu C, Guo Q, Wei R, Yin X, Zhang Y, Li X Tags: J Leukoc Biol Source Type: research

Th17 cell pathogenicity and plasticity in rheumatoid arthritis.
Abstract CD4+ Th cells play an important role in the development of rheumatoid arthritis (RA) by regulating adaptive immune response. As major subsets of CD4+ Th cells, Th17 cells can produce a large number of hallmark cytokines such as IL-17A and IL-17F, which participate in host defense and immune homeostasis. However, increasing researches have shown that Th17 cells are unstable and exhibit a certain degree of plasticity, which aggravates their pathogenicity. Furthermore, the plasticity and pathogenicity of Th17 cells are closely related with the disease activity in RA. In this paper, the characteristics includ...
Source: Journal of Leukocyte Biology - September 9, 2019 Category: Hematology Authors: Yang P, Qian FY, Zhang MF, Xu AL, Wang X, Jiang BP, Zhou LL Tags: J Leukoc Biol Source Type: research

Functional evolution of the colony-stimulating factor 1 receptor (CSF1R) and its ligands in birds.
Abstract Macrophage colony-stimulating factor (CSF1 or M-CSF) and interleukin 34 (IL34) are secreted cytokines that control macrophage survival and differentiation. Both act through the CSF1 receptor (CSF1R), a type III transmembrane receptor tyrosine kinase. The functions of CSF1R and both ligands are conserved in birds. We have analyzed protein-coding sequence divergence among avian species. The intracellular tyrosine kinase domain of CSF1R was highly conserved in bird species as in mammals but the extracellular domain of avian CSF1R was more divergent in birds with multiple positively selected amino acids. Base...
Source: Journal of Leukocyte Biology - September 5, 2019 Category: Hematology Authors: Hume DA, Gutowska-Ding MW, Garcia-Morales C, Kebede A, Bamidele O, Trujillo AV, Gheyas AA, Smith J Tags: J Leukoc Biol Source Type: research

CD56- CD16+ NK cells from HIV-infected individuals negatively regulate IFN- γ production by autologous CD8+ T cells.
CD56- CD16+ NK cells from HIV-infected individuals negatively regulate IFN-γ production by autologous CD8+ T cells. J Leukoc Biol. 2019 Sep 04;: Authors: Ma M, Yin X, Zhao X, Guo C, Zhu X, Liu T, Yang M, Zhang Z, Fu Y, Liu J, Xu J, Ding H, Han X, Chu Z, Shang H, Jiang Y Abstract The percentage of human CD56- CD16+ NK cells increases during chronic infection with human HIV; however, the biologic role of CD56- CD16+ NK cells in HIV infection is unclear. Our results demonstrate that the percentage of CD56- CD16+ NK cells producing IL-10 and TGF-β was higher than CD56dim CD16+ NK cells. CD56- C...
Source: Journal of Leukocyte Biology - September 4, 2019 Category: Hematology Authors: Ma M, Yin X, Zhao X, Guo C, Zhu X, Liu T, Yang M, Zhang Z, Fu Y, Liu J, Xu J, Ding H, Han X, Chu Z, Shang H, Jiang Y Tags: J Leukoc Biol Source Type: research

Impact of pregravid obesity on maternal and fetal immunity: Fertile grounds for reprogramming.
Abstract Maternal pregravid obesity results in several adverse health outcomes during pregnancy, including increased risk of gestational diabetes, preeclampsia, placental abruption, and complications at delivery. Additionally, pregravid obesity and in utero exposure to high fat diet have been shown to have detrimental effects on fetal programming, predisposing the offspring to adverse cardiometabolic, endocrine, and neurodevelopmental outcomes. More recently, a deeper appreciation for the modulation of offspring immunity and infectious disease-related outcomes by maternal pregravid obesity has emerged. This review...
Source: Journal of Leukocyte Biology - September 4, 2019 Category: Hematology Authors: Sureshchandra S, Marshall NE, Messaoudi I Tags: J Leukoc Biol Source Type: research

Mac-1 triggers neutrophil DNA extracellular trap formation to Aspergillus fumigatus independently of PAD4 histone citrullination.
Abstract Aspergillus fumigatus (A. fumigatus) is an environmental fungus and a human pathogen. Neutrophils are critical effector cells during the fungal infections, and neutropenia is a risk factor for the development of pulmonary aspergillosis. Neutrophil extracellular traps (NETs) are released by neutrophils in response to A. fumigatus and inhibit the conidial germination. In this work, we observed that the receptors TLR2, TLR4, and Dectin-1 were dispensable for the A. fumigatus induced NET release. In contrast CD11b/CD18 was critical for the NET release in response to A. fumigatus conidia, and this required the...
Source: Journal of Leukocyte Biology - September 2, 2019 Category: Hematology Authors: Silva JC, Rodrigues NC, Thompson-Souza GA, Muniz VS, Neves JS, Figueiredo RT Tags: J Leukoc Biol Source Type: research

Treatment with DNases rescues hidden neutrophil elastase from aggregated NETs.
Schauer C Abstract The release of neutrophil extracellular traps (NETs) is one of the weapons neutrophils have in their armory. NETs consist of extracellular chromatin fibers decorated with a plethora of cytoplasmic and granular proteins, such as the antimicrobial serine protease neutrophil elastase (NE). Because the first description of NETs as beneficial to the host, reports on their double-faced role in health and disease have considerably increased recently. On one hand, NETs reportedly trap and kill bacteria and also participate in the resolution of the acute inflammation associated with infection and with ti...
Source: Journal of Leukocyte Biology - September 2, 2019 Category: Hematology Authors: Podolska MJ, Mahajan A, Hahn J, Knopf J, Maueröder C, Petru L, Ullmann M, Schett G, Leppkes M, Herrmann M, Muñoz LE, Schauer C Tags: J Leukoc Biol Source Type: research

Frontline Science: A flexible kink in the transmembrane domain impairs β2 integrin extension and cell arrest from rolling.
Frontline Science: A flexible kink in the transmembrane domain impairs β2 integrin extension and cell arrest from rolling. J Leukoc Biol. 2019 Sep 01;: Authors: Sun H, Fan Z, Gingras AR, Lopez-Ramirez MA, Ginsberg MH, Ley K Abstract β2 integrins are the main adhesion molecules in neutrophils and other leukocytes and are rapidly activated by inside-out signaling, which results in conformational changes that are transmitted through the transmembrane domain (TMD). Here, we investigated the biologic effect of introducing a proline mutation in the β2 integrin TMD to create a flexible kink th...
Source: Journal of Leukocyte Biology - September 1, 2019 Category: Hematology Authors: Sun H, Fan Z, Gingras AR, Lopez-Ramirez MA, Ginsberg MH, Ley K Tags: J Leukoc Biol Source Type: research

SCIMP is a universal Toll-like receptor adaptor in macrophages.
We report here that SCIMP is phosphorylated and activated in response to agonists of multiple TLRs, including TLR2, TLR3, TLR4, and TLR9. SCIMP also interacts with TLRs that are known to signal from both the cell surface and endosomal compartments. In so doing, this transmembrane adaptor presents Lyn, along with other effectors such as Grb2, Csk, and SLP65, to multiple TLRs during cellular activation. CRISPR-mediated knockout or silencing of SCIMP in macrophages alters TLR signaling outputs and the production of IL-6 and IL-12p40 downstream of multiple TLRs, and upon challenge with live bacteria. Furthermore, the selectivi...
Source: Journal of Leukocyte Biology - August 29, 2019 Category: Hematology Authors: Luo L, Curson JEB, Liu L, Wall AA, Tuladhar N, Lucas RM, Sweet MJ, Stow JL Tags: J Leukoc Biol Source Type: research

At the bench: Engineering the next generation of cancer vaccines.
Abstract Cancer vaccines hold promise as an immunotherapeutic modality based on their potential to generate tumor antigen-specific T cell responses and long-lived antitumor responses capable of combating metastatic disease and recurrence. However, cancer vaccines have historically failed to deliver significant therapeutic benefit in the clinic, which we maintain is due in part to drug delivery challenges that have limited vaccine immunogenicity and efficacy. In this review, we examine some of the known and putative failure mechanisms of common first-generation clinical cancer vaccines, and describe how the rationa...
Source: Journal of Leukocyte Biology - August 20, 2019 Category: Hematology Authors: Shae D, Baljon JJ, Wehbe M, Becker KW, Sheehy TL, Wilson JT Tags: J Leukoc Biol Source Type: research

Prolonged exposure to hypoxia induces an autophagy-like cell survival program in human neutrophils.
Abstract Neutrophils contribute to low oxygen availability at inflammatory sites through the generation of reactive oxidants. They are also functionally affected by hypoxia, which delays neutrophil apoptosis. However, the eventual fate of neutrophils in hypoxic conditions is unknown and this is important for their effective clearance and the resolution of inflammation. We have monitored the survival and function of normal human neutrophils exposed to hypoxia over a 48 h period. Apoptosis was delayed, and the cells remained intact even at 48 h. However, hypoxia promoted significant changes in neutrophil morphology ...
Source: Journal of Leukocyte Biology - August 14, 2019 Category: Hematology Authors: Talla U, Bozonet SM, Parker HA, Hampton MB, Vissers MCM Tags: J Leukoc Biol Source Type: research

Phosphoinositide-3 kinase gamma regulates caspase-1 activation and leukocyte recruitment in acute murine gout.
This study investigates the participation of PI3Kγ in the development of joint inflammation and dysfunction in an experimental model of acute gout in mice. Acute gout was induced by injection of monosodium urate (MSU) crystals into the tibiofemoral joint of mice. The involvement of PI3Kγ was evaluated using a selective inhibitor and mice deficient for PI3Kγ (PI3Kγ-/- ) or with loss of kinase activity. Neutrophils recovered from the inflamed joint were quantified and stained for phosphorylated Akt (pAkt) and production of reactive oxygen species (ROS). The adherence of leukocytes to the joint microva...
Source: Journal of Leukocyte Biology - August 8, 2019 Category: Hematology Authors: Tavares LD, Galvão I, Costa VV, Batista NV, Rossi LCR, Brito CB, Reis AC, Queiroz-Junior CM, Braga AD, Coelho FM, Dias AC, Zamboni DS, Pinho V, Teixeira MM, Amaral FA, Souza DG Tags: J Leukoc Biol Source Type: research

Frontline Science: Escherichia coli use LPS as decoy to impair neutrophil chemotaxis and defeat antimicrobial host defense.
Abstract Bacterial infections and sepsis are leading causes of morbidity and mortality in critically ill patients. Currently, there are no effective treatments available to improve clinical outcome in sepsis. Here, we elucidated a mechanism by which Escherichia coli (E. coli) bacteria impair neutrophil (PMN) chemotaxis and we studied whether this mechanism can be therapeutically targeted to improve chemotaxis and antimicrobial host defense. PMNs detect bacteria with formyl peptide receptors (FPR). FPR stimulation triggers mitochondrial ATP production and release. Autocrine stimulation of purinergic receptors exert...
Source: Journal of Leukocyte Biology - August 8, 2019 Category: Hematology Authors: Kondo Y, Ledderose C, Slubowski CJ, Fakhari M, Sumi Y, Sueyoshi K, Bezler AK, Aytan D, Arbab M, Junger WG Tags: J Leukoc Biol Source Type: research

Analysis of the impact of CSF-1 administration in adult rats using a novel Csf1r-mApple reporter gene.
Abstract Macrophages are present in large numbers in every tissue in the body where they play critical roles in development and homeostasis. They exhibit remarkable phenotypic and functional diversity, underpinning their adaptation to specialized roles in each tissue niche. CSF1, signaling through the CSF1 receptor, which is restricted to monocyte-macrophage lineage cells in adults, is a critical growth factor controlling macrophage proliferation, differentiation, and many aspects of mature macrophage function. We have generated a macrophage reporter rat, utilizing a construct containing elements of the mouse Csf1...
Source: Journal of Leukocyte Biology - August 8, 2019 Category: Hematology Authors: Irvine KM, Caruso M, Cestari MF, Davis GM, Keshvari S, Sehgal A, Pridans C, Hume DA Tags: J Leukoc Biol Source Type: research

A shift toward inhibitory receptors and impaired effector functions on NK cells contribute to immunosuppression during sepsis.
In this study, we aimed to decipher NK cell immunity of septic patients in a more comprehensive way. We found that cytotoxicity of NK cells dramatically decreased during sepsis, likely due to the reduction of cluster of differentiation (CD)3- CD56+ NK cells and a shift of phenotypic changes of NK group 2 member (NKG2) receptors, natural cytotoxicity receptors (NCRs) and killer immunoglobulin-like receptors (KIRs) toward inhibitory receptors demonstrated by CD3- CD56+ NK cells in septic patients. Expression of the activation indicator CD69 and cytotoxic associated marker CD107a on CD3- CD56+ NK cells in healthy adults was s...
Source: Journal of Leukocyte Biology - August 6, 2019 Category: Hematology Authors: Feng T, Liao X, Yang X, Yang C, Lin F, Guo Y, Kang Y, Li H Tags: J Leukoc Biol Source Type: research

The upside-downside nature of Vitamin D signaling in liver.
PMID: 31379001 [PubMed - as supplied by publisher] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - August 5, 2019 Category: Hematology Authors: Scott MJ Tags: J Leukoc Biol Source Type: research

Living on the edge: Pain control by blood leukocytes at the borders of the central nervous system.
Discussion on the impact of blood leukocytes accumulating at the borders of the central nervous system on the development of neuropathic pain. PMID: 31378970 [PubMed - as supplied by publisher] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - August 4, 2019 Category: Hematology Authors: Pinho-Ribeiro FA Tags: J Leukoc Biol Source Type: research

IL-32 and its splice variants are associated with protection against  Mycobacterium tuberculosis infection and skewing of Th1/Th17 cytokines.
IL-32 and its splice variants are associated with protection against Mycobacterium tuberculosis infection and skewing of Th1/Th17 cytokines. J Leukoc Biol. 2019 Aug 04;: Authors: Koeken VACM, Verrall AJ, Ardiansyah E, Apriani L, Dos Santos JC, Kumar V, Alisjahbana B, Hill PC, Joosten LAB, van Crevel R, van Laarhoven A Abstract Studies in IL-32 transgenic mice and in vitro suggest that IL-32 may have protective effects against Mycobacterium tuberculosis, but so far there are barely any studies in humans. We studied the role of IL-32 and its splice variants in tuberculosis (TB) in vivo and in ...
Source: Journal of Leukocyte Biology - August 4, 2019 Category: Hematology Authors: Koeken VACM, Verrall AJ, Ardiansyah E, Apriani L, Dos Santos JC, Kumar V, Alisjahbana B, Hill PC, Joosten LAB, van Crevel R, van Laarhoven A Tags: J Leukoc Biol Source Type: research

Frontline Science: Exhaustion and senescence marker profiles on human T cells in BRGSF-A2  humanized mice resemble those in human samples.
Frontline Science: Exhaustion and senescence marker profiles on human T cells in BRGSF-A2 humanized mice resemble those in human samples. J Leukoc Biol. 2019 Aug 04;: Authors: Labarthe L, Henriquez S, Lambotte O, Di Santo JP, Le Grand R, Pflumio F, Arcangeli ML, Legrand N, Bourgeois C Abstract This work sought to confirm the human-like expression of exhaustion and senescence markers in a mouse model with a humanized immune system (HIS): the Balb/c Rag2KO IL2rgcKO SirpαNOD Flk2KO HLA-A2HHD (BRGSF-A2) mouse reconstituted with human CD34+ cord blood cells. With regard to senescence markers, th...
Source: Journal of Leukocyte Biology - August 4, 2019 Category: Hematology Authors: Labarthe L, Henriquez S, Lambotte O, Di Santo JP, Le Grand R, Pflumio F, Arcangeli ML, Legrand N, Bourgeois C Tags: J Leukoc Biol Source Type: research

Frontline Science: Rev-Erb α links blue light with enhanced bacterial clearance and improved survival in murine Klebsiella pneumoniae pneumonia.
Frontline Science: Rev-Erbα links blue light with enhanced bacterial clearance and improved survival in murine Klebsiella pneumoniae pneumonia. J Leukoc Biol. 2019 Aug 04;: Authors: Griepentrog JE, Zhang X, Lewis AJ, Gianfrate G, Labiner HE, Zou B, Xiong Z, Lee JS, Rosengart MR Abstract The wavelength of light is a critical determinant of light's capacity to entrain adaptive biological mechanisms, such as enhanced immune surveillance, that precede and prepare us for the active circadian day, a time when the risk of encountering pathogen is highest. Light rich in the shorter wavelength visible bl...
Source: Journal of Leukocyte Biology - August 4, 2019 Category: Hematology Authors: Griepentrog JE, Zhang X, Lewis AJ, Gianfrate G, Labiner HE, Zou B, Xiong Z, Lee JS, Rosengart MR Tags: J Leukoc Biol Source Type: research

Connecting the dots in type 1 diabetes: The role for gut-pancreas axis.
Discussion on changes in gut microbiota driving the breakdown of mucosal barrier in NOD mice; the resulting inflammation and impairment of oral tolerance induces the autoimmune diabetes. PMID: 31369695 [PubMed - as supplied by publisher] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - August 1, 2019 Category: Hematology Authors: Menezes-Silva L, Fonseca DMD Tags: J Leukoc Biol Source Type: research

Novel functions of inactive rhomboid proteins in immunity and disease.
Abstract iRhoms are related to a family of intramembrane serine proteinases called rhomboids but lack proteolytic activity. In mammals, there are two iRhoms, iRhom1 and iRhom2, which have similar domain structures and overlapping specificities as well as distinctive functions. These catalytically inactive rhomboids are essential regulators for the maturation and trafficking of the disintegrin metalloprotease ADAM17 from the endoplasmic reticulum to the cell surface, and are required for the cleavage and release of a variety of membrane-associated proteins, including the IL-6 receptor, l-selectin, TNF, and EGFR lig...
Source: Journal of Leukocyte Biology - August 1, 2019 Category: Hematology Authors: Geesala R, Issuree PD, Maretzky T Tags: J Leukoc Biol Source Type: research

Resolution of inflammation: Role of B cells.
Discussion on pro-resolving lipid mediators in obesity: role of B cells. PMID: 31344281 [PubMed - in process] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - July 27, 2019 Category: Hematology Authors: Libreros S Tags: J Leukoc Biol Source Type: research

Lysophosphatidic acid up-regulates IL-10 production to inhibit TNF- α synthesis in Mϕs stimulated with LPS.
In this report, we show that LPA strongly inhibits the LPS-induced TNF-α production at the mRNA and protein levels in primary Mϕs and Mϕ-like J774 cells. The decreased TNF-α production in LPA/LPS-stimulated cells is to high extent independent of NF-κB but is preceded by enhanced expression and secretion of the anti-inflammatory cytokine IL-10. The IL-10 elevation and TNF-α reduction are both abrogated upon depletion of the LPA5 and LPA6 receptors in J774 cells and can be linked with LPA-mediated activation of p38. We propose that the binding of LPA to LPA5 and LPA6 fine-tunes the LPS-induced infla...
Source: Journal of Leukocyte Biology - July 23, 2019 Category: Hematology Authors: Ciesielska A, Hromada-Judycka A, Ziemlińska E, Kwiatkowska K Tags: J Leukoc Biol Source Type: research

TLR9 agonist adsorbed to alum adjuvant prevents asthma-like responses induced by Blomia tropicalis mite extract.
sso M Abstract Blomia tropicalis mite is highly prevalent in tropical and subtropical regions and it is associated with allergic diseases such as rhinitis and asthma. By using an OVA-model of allergic lung disease, we have previously shown that sensitization in the presence of toll like receptors (TLRs) agonists attenuates subsequent OVA-induced allergic responses. Here, we evaluated the effect of CpG-ODN, a specific synthetic TLR-9 agonist, on the development of experimental asthma induced by Blomia tropicalis extract, a relevant source of aeroallergens. Among different protocols of Blomia tropicalis extract sens...
Source: Journal of Leukocyte Biology - July 22, 2019 Category: Hematology Authors: Nunes FPB, Alberca-Custódio RW, Gomes E, Fonseca DM, Yokoyama NH, Labrada A, Russo M Tags: J Leukoc Biol Source Type: research

Quantitative proteomic analyses in blood: A window to human health and disease.
Abstract This review discusses how the measurement of proteins in blood and its components via quantitative proteomics analyses can inform health status. Various external and internal factors such as environmental conditions, genetic background, nutrition, diet, and lifestyle, chronic pathological conditions, disease state, or therapeutic intervention will be investigated and their effects on the protein profile will be shown. The resulting changes to ones' health and how this protein expression information can be used in early screening/diagnostic applications, drug discovery, precision treatment, patient managem...
Source: Journal of Leukocyte Biology - July 22, 2019 Category: Hematology Authors: Whittaker K, Burgess R, Jones V, Yang Y, Zhou W, Luo S, Wilson J, Huang RP Tags: J Leukoc Biol Source Type: research

Phenotypic impacts of CSF1R deficiencies in humans and model organisms.
Abstract Mϕ proliferation, differentiation, and survival are controlled by signals from the Mϕ CSF receptor (CSF1R). Mono-allelic gain-of-function mutations in CSF1R in humans are associated with an autosomal-dominant leukodystrophy and bi-allelic loss-of-function mutations with recessive skeletal dysplasia, brain disorders, and developmental anomalies. Most of the phenotypes observed in these human disease states are also observed in mice and rats with loss-of-function mutations in Csf1r or in Csf1 encoding one of its two ligands. Studies in rodent models also highlight the importance of genetic background and ...
Source: Journal of Leukocyte Biology - July 22, 2019 Category: Hematology Authors: Hume DA, Caruso M, Ferrari-Cestari M, Summers KM, Pridans C, Irvine KM Tags: J Leukoc Biol Source Type: research

Malt1 deficient mice develop osteoporosis independent of osteoclast-intrinsic effects of Malt1 deficiency.
This study tested the hypothesis that mucosa associated lymphoid tissue 1 (Malt1) deficiency causes osteoporosis in mice by increasing osteoclastogenesis and osteoclast activity. A patient with combined immunodeficiency (CID) caused by MALT1 deficiency had low bone mineral density resulting in multiple low impact fractures that was corrected by hematopoietic stem cell transplant (HSCT). We have reported that Malt1 deficient Mϕs, another myeloid cell type, are hyper-responsive to inflammatory stimuli. Our objectives were to determine whether Malt1 deficient mice develop an osteoporosis-like phenotype and whether it was cau...
Source: Journal of Leukocyte Biology - July 16, 2019 Category: Hematology Authors: Monajemi M, Fisk S, Pang YCF, Leung J, Menzies SC, Ben-Othman R, Cai B, Kollmann TR, Rozmus J, Sly LM Tags: J Leukoc Biol Source Type: research

Frontline Science: Abnormalities in the gut mucosa of non-obese diabetic mice precede the onset of type 1 diabetes.
Faria AMC Abstract Alterations in the composition of the intestinal microbiota have been associated with development of type 1 diabetes (T1D), but little is known about changes in intestinal homeostasis that contribute to disease pathogenesis. Here, we analyzed oral tolerance induction, components of the intestinal barrier, fecal microbiota, and immune cell phenotypes in non-obese diabetic (NOD) mice during disease progression compared to non-obese diabetes resistant (NOR) mice. NOD mice failed to develop oral tolerance and had defective protective/regulatory mechanisms in the intestinal mucosa, including de...
Source: Journal of Leukocyte Biology - July 16, 2019 Category: Hematology Authors: Miranda MCG, Oliveira RP, Torres L, Aguiar SLF, Pinheiro-Rosa N, Lemos L, Guimarães MA, Reis D, Silveira T, Ferreira Ê, Moreira TG, Cara DC, Maioli TU, Kelsall BL, Carlos D, Faria AMC Tags: J Leukoc Biol Source Type: research

JAK inhibition by methotrexate (and csDMARDs) may explain clinical efficacy as monotherapy and combination therapy.
Abstract Methotrexate (MTX) is recognized as the anchor drug in the algorithm treating chronic arthritis (RA, psoriatic arthritis), as well as a steroid sparing agent in other inflammatory conditions (polymyalgia rheumatica, vasculitis, scleroderma). Its main mechanism of action has been related to the increase in extracellular adenosine, which leads to the effects of A2A receptor in M1 macrophages that dampens TNFα and IL12 production and increases IL1Ra and TNFRp75. By acting on A2B receptor on M2 macrophages it enhances IL10 synthesis and inhibits NF-kB signaling. MTX has also been shown to exert JAK inhi...
Source: Journal of Leukocyte Biology - July 16, 2019 Category: Hematology Authors: Gremese E, Alivernini S, Tolusso B, Zeidler MP, Ferraccioli G Tags: J Leukoc Biol Source Type: research

Sensitivity of Kupffer cells and liver sinusoidal endothelial cells to ricin toxin and ricin toxin-Ab complexes.
In this report, we investigated the capacity of a collection of ricin-specific mouse MAb and camelid single-domain (VH H) antibodies to protect KCs and LSECs from ricin-induced killing. In the case of KCs, individual MAbs against RTA or RTB afforded near complete protection against ricin in ex vivo and in vivo challenge studies. In contrast, individual MAbs or VH Hs afforded little (
Source: Journal of Leukocyte Biology - July 16, 2019 Category: Hematology Authors: Mooney B, Torres-Velez FJ, Doering J, Ehrbar DJ, Mantis NJ Tags: J Leukoc Biol Source Type: research

Secreted IgM: New tricks for an old molecule.
Abstract Secreted IgM (sIgM) is a multifunctional evolutionary conserved antibody that is critical for the maintenance of tissue homeostasis as well as the development of fully protective humoral responses to pathogens. Constitutive secretion of self- and polyreactive natural IgM, produced mainly by B-1 cells, provides a circulating antibody that engages with autoantigens as well as invading pathogens, removing apoptotic and other cell debris and initiating strong immune responses. Pathogen-induced IgM production by B-1 and conventional B-2 cells strengthens this early, passive layer of IgM-mediated immune defense...
Source: Journal of Leukocyte Biology - July 14, 2019 Category: Hematology Authors: Blandino R, Baumgarth N Tags: J Leukoc Biol Source Type: research

The function of P-selectin glycoprotein ligand-1 is conserved from ancestral fishes to mammals.
i O Abstract PSGL-1 is a mucin-like glycoprotein that supports, in mammals, leukocyte rolling on selectins. However, we have limited knowledge whether its function is conserved in non-mammals and how its structure adapted during evolution. To identify conserved amino acid sequences required for selectin binding, we performed multiple alignments of PSGL-1 sequences from 18 mammals, 4 birds, 3 reptiles, 1 amphibian, and 15 fishes. The amino-terminal T[D/E]PP[D/E] motif, which identifies in mammals a core-2 O-glycosylated threonine required for selectin-binding, is partially conserved in some fishes (e.g., T. rubripe...
Source: Journal of Leukocyte Biology - July 14, 2019 Category: Hematology Authors: Baïsse B, Spertini C, Galisson F, Smirnova T, Spertini O Tags: J Leukoc Biol Source Type: research

Novel MRGPRX2 antagonists inhibit IgE-independent activation of human umbilical cord blood-derived mast cells.
This study strongly suggests that MRGPRX2 antagonists may be a promising drug to prevent the IgE-independent allergic reactions, and thus, MRGPRX2 antagonist development may lead to a promising therapeutic medication for the IgE-independent allergic reactions. PMID: 31299111 [PubMed - as supplied by publisher] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - July 12, 2019 Category: Hematology Authors: Ogasawara H, Furuno M, Edamura K, Noguchi M Tags: J Leukoc Biol Source Type: research

Deregulation of Ikaros expression in B-1 cells: New insights in the malignant transformation to chronic lymphocytic leukemia.
Abstract Chronic lymphocytic leukemia (CLL) is a chronic form of leukemia that originates from an abnormal expansion of CD5+ B-1 cells. Deregulation in the BCR signaling is associated with B-cell transformation. Contrariwise to B-2 cells, BCR engagement in B-1 cells results in low proliferation rate and increased apoptosis population, whereas overactivation may be associated with lymphoproliferative disorders. It has been demonstrated that several transcription factors that are involved in the B cell development play a role in the regulation of BCR function. Among them, Ikaros is considered an essential regulator ...
Source: Journal of Leukocyte Biology - July 12, 2019 Category: Hematology Authors: Oliveira VC, Lacerda MP, Moraes BBM, Gomes CP, Maricato JT, Souza OF, Schenkman S, Pesquero JB, Moretti NS, Rodrigues CA, Popi AF Tags: J Leukoc Biol Source Type: research