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https://www.readbyqxmd.com/read/28822770/regulation-of-autoimmune-myocarditis-by-host-responses-to-the-microbiome
#1
Jobert G Barin, Monica V Talor, Nicola L Diny, SuFey Ong, Julie A Schaub, Elizabeth Gebremariam, Djahida Bedja, Guobao Chen, Hee Sun Choi, Xuezhou Hou, Lei Wu, Ashley B Cardamone, Daniel A Peterson, Noel R Rose, Daniela Čiháková
The extensive, diverse communities that constitute the microbiome are increasingly appreciated as important regulators of human health and disease through inflammatory, immune, and metabolic pathways. We sought to elucidate pathways by which microbiota contribute to inflammatory, autoimmune cardiac disease. We employed an animal model of experimental autoimmune myocarditis (EAM), which results in inflammatory and autoimmune pathophysiology and subsequent maladaptive cardiac remodeling and heart failure. Antibiotic dysbiosis protected mice from EAM and fibrotic cardiac dysfunction...
August 16, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28807771/increase-of-intermediate-monocytes-in-gvhd-correlation-with-mdr1-th17-1-levels-and-the-effect-of-prednisolone-and-1%C3%AE-25-dihydroxyvitamin-d3
#2
Katharina Reinhardt-Heller, Insa Hirschberg, Peter Lang, Thomas Vogl, Rupert Handgretinger, Wolfgang A Bethge, Ursula Holzer
Graft-versus-host disease (GvHD) remains one of the major complications after allogeneic hematopoietic stem cell transplantation which is mainly treated with glucocorticoids such as prednisolone. In this study, the influence of monocyte subpopulations, prednisolone and 1α,25-Dihydroxyvitamin D3 on the induction of a pro-inflammatory subset of Th17 cells (MDR(+)Th17.1) characterized by CCR6(+)CXCR3(hi)CCR4(lo)CCR10(-)CD161(+) and stable expression of the multi-drug resistance protein type 1 (MDR1) was investigated...
August 11, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28806403/th17-cells-are-associated-with-protection-from-ventilator-associated-pneumonia
#3
Marika Orlov, Victoria Dmyterko, Mark M Wurfel, Carmen Mikacenic
BACKGROUND: CD4+ T-helper 17 (Th17) cells and Interleukin (IL)-17A play an important role in clearing pathogens in mouse models of pneumonia. We hypothesized that numbers of Th17 cells and levels of IL-17A are associated with risk for nosocomial pneumonia in humans. METHODS: We collected bronchoalveolar lavage (BAL) fluid from mechanically ventilated (n = 25) patients undergoing quantitative bacterial culture to evaluate for ventilator associated pneumonia (VAP)...
2017: PloS One
https://www.readbyqxmd.com/read/28798316/the-proton-sensing-g-protein-coupled-receptor-t-cell-death-associated-gene-8-tdag8-shows-cardioprotective-effects-against-myocardial-infarction
#4
Akiomi Nagasaka, Chihiro Mogi, Hiroki Ono, Toshihide Nishi, Yuma Horii, Yuki Ohba, Koichi Sato, Michio Nakaya, Fumikazu Okajima, Hitoshi Kurose
Myocardial infarction (MI) is an ischaemic heart condition caused by the occlusion of coronary arteries. Following MI, lactic acid from anaerobic glycolysis increases and infiltrating immune cells produce severe inflammation, which leads to acidosis in the ischaemic heart. However, the physiological implication of this pH reduction remains largely unknown. T-cell death-associated gene 8 (TDAG8) is a proton-sensing G protein-coupled receptor found on cardiac macrophages that recognise increases in extracellular protons...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794233/characterization-of-mycobacterium-tuberculosis-specific-cells-using-mhc-class-ii-tetramers-reveals-phenotypic-differences-related-to-hiv-infection-and-tuberculosis-disease
#5
Natalie Strickland, Tracey L Müller, Natacha Berkowitz, Rene Goliath, Mary N Carrington, Robert J Wilkinson, Wendy A Burgers, Catherine Riou
A major challenge for the development of an effective vaccine against tuberculosis (TB) is that the attributes of protective CD4(+) T cell responses are still elusive for human TB. Infection with HIV type 1 is a major risk factor for TB, and a better understanding of HIV-induced alterations of Mycobacterium tuberculosis-specific CD4(+) T cells that leads to failed host resistance may provide insight into protective T cell immunity to TB. A total of 86 participants from a TB-endemic setting, either HIV-infected or uninfected and with latent or active TB (aTB), were screened using M...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28783702/natural-killer-cell-mediated-inflammation-resolution-is-disabled-in-severe-asthma
#6
Melody G Duvall, Cindy Barnig, Manuela Cernadas, Isabell Ricklefs, Nandini Krishnamoorthy, Nicole L Grossman, Nirav R Bhakta, John V Fahy, Eugene R Bleecker, Mario Castro, Serpil C Erzurum, Benjamin M Gaston, Nizar N Jarjour, David T Mauger, Sally E Wenzel, Suzy A Comhair, Andrea M Coverstone, Merritt L Fajt, Annette T Hastie, Mats W Johansson, Michael C Peters, Brenda R Phillips, Elliot Israel, Bruce D Levy
Severe asthma is typically characterized by chronic airway inflammation that is refractory to corticosteroids and associated with excess morbidity. Patients were recruited into the National Heart, Lung, and Blood Institute-sponsored Severe Asthma Research Program and comprehensively phenotyped by bronchoscopy. Bronchoalveolar lavage (BAL) cells were analyzed by flow cytometry. Compared with healthy individuals (n = 21), patients with asthma (n = 53) had fewer BAL natural killer (NK) cells. Patients with severe asthma (n = 29) had a marked increase in the ratios of CD4(+) T cells to NK cells and neutrophils to NK cells...
March 10, 2017: Science Immunology
https://www.readbyqxmd.com/read/28781371/t-helper-type-17-cells-in-immune-mediated-glomerular-disease
#7
REVIEW
Christian F Krebs, Tilman Schmidt, Jan-Hendrik Riedel, Ulf Panzer
CD4(+) T cells are important drivers of tissue damage in immune-mediated renal diseases, such as anti-glomerular basement membrane glomerulonephritis, anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis. The discovery of a distinct, IL-17-producing CD4(+) T-cell lineage termed T helper type 17 (TH17) cells has markedly advanced current understanding of the pathogenic mechanisms of organ-specific immunity and the pathways that lead to target organ damage. TH17 cells are characterized by the expression of the transcription factor RORγt, the production of the pro-inflammatory cytokines IL-17A, IL-17F, IL-22, and high expression of the chemokine receptor C-C-motif chemokine receptor 6 (CCR6)...
August 7, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28780305/activated-hepatic-stellate-cells-directly-induce-pathogenic-th17-cells-in-chronic-hepatitis-b-virus-infection
#8
Yun Liu, Lei Li, Jiang Liu, Wei-Min She, Jie-Min Shi, Jing Li, Ji-Yao Wang, Wei Jiang
Th17 cells are involved in liver fibrosis by activating hepatic stellate cells (HSCs). We aimed to investigate whether HSCs are able to regulate the function of Th17 cells and to determine the relevant mechanism. Sixty-five patients diagnosed with chronic hepatitis B (CHB) were enrolled in this study. To determine the effect of HSCs on T cells, naïve CD4(+)T cells and Th17 cells were sorted from CHB patients and cultured with or without activated-HSCs, and cytokine expression and gene transcription were analyzed...
August 2, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28778069/zbtb1-controls-nkp46-ror-gamma-t-innate-lymphoid-cell-ilc3-development
#9
Ying Lu, Xianyu Zhang, Nicolas Bouladoux, Saransh Neel Kaul, Kangxin Jin, Derek Sant'Angelo, Yasmine Belkaid, Damian Kovalovsky
Innate lymphoid cells (ILCs) play a central role conferring protection at the mucosal frontier. In this study, we have identified a requirement of the transcription factor Zbtb1 for the development of RORγt+ ILCs (ILC3s). Zbtb1-deficient mice lacked NKp46+ ILC3 cells in the lamina propria of the small and large intestine. This requirement of Zbtb1 was cell intrinsic, as NKp46+ ILC3s were not generated from Zbtb1-deficient progenitors in bone marrow chimeras and Zbtb1-deficient RORγt+ CCR6-NKp46- ILC3s didn't generate NKp46+ ILC3s in co-cultures with OP9-DL1 stroma...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28768913/hiv-1-selectively-targets-gut-homing-ccr6-cd4-t-cells-via-mtor-dependent-mechanisms
#10
Delphine Planas, Yuwei Zhang, Patricia Monteiro, Jean-Philippe Goulet, Annie Gosselin, Nathalie Grandvaux, Thomas J Hope, Ariberto Fassati, Jean-Pierre Routy, Petronela Ancuta
Gut-associated lymphoid tissues are enriched in CCR6+ Th17-polarized CD4+ T cells that contribute to HIV-1 persistence during antiretroviral therapy (ART). This raises the need for Th17-targeted immunotherapies. In an effort to identify mechanisms governing HIV-1 permissiveness/persistence in gut-homing Th17 cells, we analyzed the transcriptome of CCR6+ versus CCR6- T cells exposed to the gut-homing inducer retinoic acid (RA) and performed functional validations in colon biopsies of HIV-infected individuals receiving ART (HIV+ART)...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28768901/essential-role-for-ccr6-in-certain-inflammatory-diseases-demonstrated-using-specific-antagonist-and-knockin-mice
#11
Remy Robert, Caroline Ang, Guizhi Sun, Laurent Juglair, Ee X Lim, Linda J Mason, Natalie L Payne, Claude Ca Bernard, Charles R Mackay
The chemokine receptor CCR6 marks subsets of T cells and innate lymphoid cells that produce IL-17 and IL-22, and as such may play a role in the recruitment of these cells to certain inflammatory sites. However, the precise role of CCR6 has been controversial, in part because no effective monoclonal antibody (mAb) inhibitors against this receptor exist for use in mouse models of inflammation. We circumvented this problem using transgenic mice expressing human CCR6 (hCCR6) under control of its native promoter (hCCR6-Tg/mCCR6-/-)...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28763457/ror%C3%AE-t-and-ror%C3%AE-signature-genes-in-human-th17-cells
#12
Glenda Castro, Xuejun Liu, Karen Ngo, Aimee De Leon-Tabaldo, Shanrong Zhao, Rosa Luna-Roman, Jingxue Yu, Tinghua Cao, Robert Kuhn, Patrick Wilkinson, Krystal Herman, Marina I Nelen, Jonathan Blevitt, Xiaohua Xue, Anne Fourie, Wai-Ping Fung-Leung
RORγt and RORα are transcription factors of the RAR-related orphan nuclear receptor (ROR) family. They are expressed in Th17 cells and have been suggested to play a role in Th17 differentiation. Although RORγt signature genes have been characterized in mouse Th17 cells, detailed information on its transcriptional control in human Th17 cells is limited and even less is known about RORα signature genes which have not been reported in either human or mouse T cells. In this study, global gene expression of human CD4 T cells activated under Th17 skewing conditions was profiled by RNA sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28756336/tnf%C3%AE-and-il-1%C3%AE-in-the-synovial-fluid-facilitate-mucosal-associated-invariant-t-mait-cell-migration
#13
Miok Kim, Su-Jin Yoo, Seong Wook Kang, Jaeyul Kwon, Inpyo Choi, Chang Hoon Lee
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affect the joints and inflammatory cell migration into inflamed articular sites contribute to this disease. Among the inflammatory cells, human mucosal-associated invariant T (MAIT) cells were recently recognized as critical cellular component with a pathological role in RA. However, their migratory characteristics are poorly understood. The aim of this study was to determine whether human MAIT cells preferentially traffick to inflamed synovial sites in rheumatoid arthritis patients and to elucidate the underlying mechanism...
July 27, 2017: Cytokine
https://www.readbyqxmd.com/read/28746740/ccr6-promotes-steady-state-intestinal-mononuclear-phagocyte-association-with-the-intestinal-epithelium-imprinting-and-immune-surveillance
#14
Keely G McDonald, Leroy W Wheeler, Jeremiah R McDole, Shannon Joerger, Jenny K Gustafsson, Devesha H Kulkarni, Kathryn A Knoop, Ifor R Williams, Mark J Miller, Rodney D Newberry
The intestinal lamina propria (LP) contains antigen presenting cells with features of dendritic cells (DCs) and macrophages, collectively referred to as mononuclear phagocytes (MNPs). Association of MNPs with the epithelium is implied to play an important role in multiple facets of intestinal immunity including imprinting MNPs with the ability to induce IgA production, inducing the expression of gut homing molecules on T cells, facilitating the capture of luminal antigens and microbes, and subsequent immune responses in the mesenteric lymph node (MLN)...
July 26, 2017: Immunology
https://www.readbyqxmd.com/read/28744287/ccr6-deficiency-impairs-iga-production-and-dysregulates-antimicrobial-peptide-production-altering-the-intestinal-flora
#15
Ya-Lin Lin, Peng-Peng Ip, Fang Liao
Intestinal immunity exists as a complex relationship among immune cells, epithelial cells, and microbiota. CCR6 and its ligand-CCL20 are highly expressed in intestinal mucosal tissues, such as Peyer's patches (PPs) and isolated lymphoid follicles (ILFs). In this study, we investigated the role of the CCR6-CCL20 axis in intestinal immunity under homeostatic conditions. CCR6 deficiency intrinsically affects germinal center reactions in PPs, leading to impairments in IgA class switching, IgA affinity, and IgA memory B cell production and positioning in PPs, suggesting an important role for CCR6 in T-cell-dependent IgA generation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28733202/v%C3%AE-4-%C3%AE-%C3%AE-t-cells-provide-an-early-source-of-il-17a-and-accelerate-skin-graft-rejection
#16
Yashu Li, Zhenggen Huang, Rongshuai Yan, Meixi Liu, Yang Bai, Guangping Liang, Xiaorong Zhang, Xiaohong Hu, Jian Chen, Chibing Huang, Baoyi Liu, Gaoxing Luo, Jun Wu, Weifeng He
Activated γδ T cells have been shown to accelerate allograft rejection. However, the precise role of skin-resident γδT cells and their subsets - Vγ5 (epidermis), Vγ1 and Vγ4 (dermis) - in skin graft rejection have not been identified. Here, using a male to female skin transplantation model, we demonstrated that Vγ4 T cells, rather than Vγ1 or Vγ5 T cells, accelerated skin graft rejection and that IL-17A was essential for Vγ4 T cell-mediated skin graft rejection. Moreover, we found that Vγ4 T cells were required for early IL-17A production in the transplanted area, both in skin grafts and in the host epidermis around grafts...
July 18, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28732768/molecular-characterization-and-expression-analysis-of-four-fish-specific-cc-chemokine-receptors-ccr4la-ccr4lc1-ccr4lc2-and%C3%A2-ccr11-in-rainbow-trout-oncorhynchus-mykiss
#17
Zhitao Qi, Jason W Holland, Yousheng Jiang, Christopher J Secombes, Pin Nie, Tiehui Wang
The chemokine and chemokine receptor networks regulate leukocyte trafficking, inflammation, immune cell differentiation, cancer and other biological processes. Comparative immunological studies have revealed that both chemokines and their receptors have expanded greatly in a species/lineage specific way. Of the 10 human CC chemokine receptors (CCR1-10) that bind CC chemokines, orthologues only to CCR6, 7, 9 and 10 are present in teleost fish. In this study, four fish-specific CCRs, termed as CCR4La, CCR4Lc1, CCR4Lc2 and CCR11, with a close link to human CCR1-5 and 8, in terms of amino acid homology and syntenic conservation, have been identified and characterized in rainbow trout (Oncorhynchus mykiss)...
July 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28710773/reciprocal-modulation-of-helper-th1-and-th17-cells-by-the-%C3%AE-2-adrenergic-receptor-agonist-drug-terbutaline
#18
Catalina M Carvajal Gonczi, Mahdieh Tabatabaei Shafiei, Ashley East, Erika Martire, Meagane H I Maurice-Ventouris, Peter J Darlington
Catecholamine hormones are powerful regulators of the immune system produced by the sympathetic nervous system. They regulate the adaptive immune system by altering T cell differentiation into T helper (Th) 1 and Th2 cell subsets, but the effect on Th17 cells is not known. Th17 cells, defined in part by chemokine receptor CCR6 and cytokine IL-17A, are crucial for mediating certain pathogen-specific responses, and are linked with several autoimmune diseases. We demonstrated that a proportion of human Th17 cells express β2-adrenergic receptor, a G protein coupled receptor that responds to catecholamines...
July 15, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28708859/interleukin-17a-induced-production-of-acute-serum-amyloid-a-by-keratinocytes-contributes-to-psoriasis-pathogenesis
#19
Elodie Couderc, Franck Morel, Pierre Levillain, Amandine Buffière-Morgado, Magalie Camus, Camille Paquier, Charles Bodet, Jean-François Jégou, Mathilde Pohin, Laure Favot, Martine Garcia, Vincent Huguier, Jiad Mcheik, Corinne Lacombe, Hans Yssel, Gérard Guillet, François-Xavier Bernard, Jean-Claude Lecron
BACKGROUND: Acute-serum Amyloid A (A-SAA), one of the major acute-phase proteins, is mainly produced in the liver but extra-hepatic synthesis involving the skin has been reported. Its expression is regulated by the transcription factors NF-κB, C/EBPβ, STAT3 activated by proinflammatory cytokines. OBJECTIVES: We investigated A-SAA synthesis by resting and cytokine-activated Normal Human Epidermal Keratinocytes (NHEK), and their inflammatory response to A-SAA stimulation...
2017: PloS One
https://www.readbyqxmd.com/read/28684423/the-rna-binding-protein-hur-contributes-to-neuroinflammation-by-promoting-c-c-chemokine-receptor-6-ccr6-expression-on-th17-cells
#20
Jing Chen, Jennifer L Martindale, Carole Cramer, Myriam Gorospe, Ulus Atasoy, Paul D Drew, Shiguang Yu
In both multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), the C C chemokine receptor 6 (CCR6) is critical for pathogenic T helper 17 (Th17) cell migration to the central nervous system (CNS). While many cytokines and their receptors are potently regulated via posttranscriptional mechanisms in response to various stimuli, how CCR6 expression is posttranscriptionally regulated in Th17 cells is unknown. Here, using RNA binding protein HuR conditional knockout (KO) and wild type (WT) mice, we present evidence that HuR posttranscriptionally regulates CCR6 expression by binding to and stabilizing Ccr6 mRNA and by promoting CCR6 translation...
July 6, 2017: Journal of Biological Chemistry
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