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TH17 T cells

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https://www.readbyqxmd.com/read/28213589/sh479-a-betulinic-acid-derivative-ameliorates-experimental-autoimmune-encephalomyelitis-by-regulating-the-th17-treg-balance
#1
Jing Li, Ji Jing, Yang Bai, Zhen Li, Roumei Xing, Binhe Tan, Xueyun Ma, Wenwei Qiu, Changsheng Du, Bing Du, Fan Yang, Jie Tang, Stefan Siwko, Mingyao Liu, Huaqing Chen, Jian Luo
CD4+ T helper cells, especially Th17 cells, combined with immune regulatory network dysfunction, play key roles in autoimmune diseases including multiple sclerosis (MS). Betulinic acid (BA), a natural pentacyclic triterpenoid, has been reported to be involved in anti-inflammation, in particular having an inhibitory effect on pro-inflammatory cytokine IL-17 and IFN-γ production. In this study, we screened BA derivatives and found a BA derivative, SH479, which had a greater inhibitory effect on Th17 differentiation...
February 17, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28209777/cd6-as-a-potential-target-for-treating-multiple-sclerosis
#2
Yan Li, Nora G Singer, Joy Whitbred, Michael A Bowen, David A Fox, Feng Lin
CD6 was established as a marker of T cells more than three decades ago, and recent studies have identified CD6 as a risk gene for multiple sclerosis (MS), a disease in which autoreactive T cells are integrally involved. Nevertheless, the precise role of CD6 in regulating T-cell responses is controversial and its significance in the pathogenesis of various diseases remains elusive, partly due to the lack of animals engineered to alter expression of the CD6 gene. In this report, we found that CD6 KO mice showed decreased pathogenic T-cell responses, reduced spinal cord T-cell infiltration, and attenuated disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
February 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28207945/cd4-cd25-garp-tregs-display-a-compromised-suppressive-function-in-patients-with-dilated-cardiomyopathy
#3
Yuzhen Wei, Kunwu Yu, Hui Wei, Xin Su, Ruirui Zhu, Huairui Shi, Haitao Sun, Quan Luo, Wenbin Xu, Junhui Xiao, Yucheng Zhong, Qiutang Zeng
Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein -A repetitions predominant (GARP) expressed on activated CD4(+) T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4(+) CD25(+) GARP(+) regulatory T cells (Tregs) in DCM. 45 DCM patients and 46 controls were enrolled in this study. There was a significant increase in peripheral Th1 and Th17 number and their related cytokines (IFN-γ, IL-17), and an obvious decrease in Treg number, TGF-β1 levels and the expression of FOXP3 and GARP in patients with DCM as compared with controls...
February 16, 2017: Immunology
https://www.readbyqxmd.com/read/28207428/il-37-ameliorates-coxsackievirus-b3-induced-viral-myocarditis-by-modulating-the-th17-treg-immune-response
#4
Bang An, Xuefei Liu, Ge Li, Haitao Yuan
Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle with an excessively activated immune response. Numerous interventions have been investigated for the treatment of myocarditis while success is limited. Interleukin-37 (IL-37), a novel member of the IL-1 cytokine family, is a natural inhibitor of innate immunity associated with autoimmune diseases. However, the modulatory effect of IL-37 in myocarditis is unknown. In this study, we investigated the immunological regulation of IL-37 in the coxsackievirus B3-induced model of murine viral myocarditis...
February 14, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28202908/silencing-c-rel-in-macrophages-dampens-th1-and-th17-immune-responses-and-alleviates-experimental-autoimmune-encephalomyelitis-in-mice
#5
Hongling Zhang, Jiacheng Bi, Huqiang Yi, Tingting Fan, Qingguo Ruan, Lintao Cai, Youhai H Chen, Xiaochun Wan
Autoimmune Th1 and Th17 responses are critical for the development of central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Although macrophages play important roles in the development of Th1 and Th17 responses, whether modulating macrophage gene transcription can diminish Th1- and Th17 cell-induced CNS pathology is unclear. In this study, we successfully silenced the expression of the transcription factor c-Rel in macrophages of mice with EAE (including those infiltrating the CNS) using chemically modified c-Rel-specific siRNAs delivered by nanoparticles...
February 16, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28202745/plasma-levels-of-eicosapentaenoic-acid-are-associated-with-anti-tnf-responsiveness-in-rheumatoid-arthritis-and-inhibit-the-etanercept-driven-rise-in-th17-cell-differentiation-in-vitro
#6
Louisa Jeffery, Helena L Fisk, Philip C Calder, Andrew Filer, Karim Raza, Christopher D Buckley, Iain McInnes, Peter C Taylor, Benjamin A Fisher
OBJECTIVE: To determine whether levels of plasma n-3 polyunsaturated fatty acids are associated with response to antitumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA), and whether this putative effect may have its basis in altering anti-TNF-driven Th17 cell differentiation. METHODS: Plasma was collected at baseline and after 3 months of anti-TNF treatment in 22 patients with established RA, and fatty acid composition of the phosphatidylcholine (PC) component was measured...
February 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28198424/human-ido-competent-long-lived-immunoregulatory-dendritic-cells-induced-by-intracellular-pathogen-and-their-fate-in-humanized-mice
#7
Rajeev K Tyagi, Brodie Miles, Rajesh Parmar, Neeraj K Garg, Sarat K Dalai, Babak Baban, Christopher W Cutler
Targeting of myeloid-dendritic cell receptor DC-SIGN by numerous chronic infectious agents, including Porphyromonas gingivalis, is shown to drive-differentiation of monocytes into dysfunctional mDCs. These mDCs exhibit alterations of their fine-tuned homeostatic function and contribute to dysregulated immune-responses. Here, we utilize P. gingivalis mutant strains to show that pathogen-differentiated mDCs from primary human-monocytes display anti-apoptotic profile, exhibited by elevated phosphorylated-Foxo1, phosphorylated-Akt1, and decreased Bim-expression...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198366/th17-cells-express-st2-and-are-controlled-by-the-alarmin-il-33-in-the-small-intestine
#8
A Pascual-Reguant, J Bayat Sarmadi, C Baumann, R Noster, D Cirera-Salinas, C Curato, P Pelczar, S Huber, C E Zielinski, M Löhning, A E Hauser, E Esplugues
TH17 cells are major drivers of inflammation and involved in several autoimmune diseases. Tissue inflammation is a beneficial host response to infection, but it can also contribute to autoimmunity. The crosstalk between a tissue and the immune system during an inflammatory response is key for preserving tissue integrity and restoring physiological processes. However, how the inflamed tissue regulates the magnitude of an immune response by controlling pro-inflammatory T cells is not well characterized so far...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28198034/human-th17-migration-in-three-dimensional-collagen-involves-p38-mapk
#9
Maleck Kadiri, Mohamed-Amine El Azreq, Sofiane Berrazouane, Marc Boisvert, Fawzi Aoudjit
T cell migration across extracellular matrix (ECM) is an important step of the adaptive immune response but is also involved in the development of inflammatory autoimmune diseases. Currently, the molecular mechanisms regulating the motility of effector T cells in ECM are not fully understood. Activation of p38 MAPK has been implicated in T cell activation and is critical to the development of immune and inflammatory responses. In this study, we examined the implication of p38 MAPK in regulating the migration of human Th17 cells through collagen...
February 15, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28197386/deficiency-of-the-immunostimulatory-cytokine-il-21-promotes-intestinal-neoplasia-via-dysregulation-of-the-th1-th17-axis
#10
Mia Shapiro, Bisweswar Nandi, Gabriel Gonzalez, Rao H Prabhala, Hiroshi Mashimo, Qin Huang, Natasha Y Frank, Nikhil C Munshi, Jason S Gold
IL-21 has reported activity in promoting both Th1 and Th17 immune responses. Its role in sporadic human colorectal cancer is unknown. We aimed to delineate the role of IL-21 in a model of sporadic intestinal carcinogenesis. We found that in APC(MIN/+) mice, ablation of IL-21 increased intestinal tumorigenesis. Expression of pro-inflammatory Th17-associated genes, including RORγt and IL-17A, was increased in the intestine in the absence of IL-21, while expression of antitumor Th1-associated genes Tbet, IFNγ, granzyme B, and perforin was decreased...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196884/functional-genomics-analysis-of-vitamin-d-effects-on-cd4-t-cells-in-vivo-in-experimental-autoimmune-encephalomyelitis-%C3%A2
#11
Manuel Zeitelhofer, Milena Z Adzemovic, David Gomez-Cabrero, Petra Bergman, Sonja Hochmeister, Marie N'diaye, Atul Paulson, Sabrina Ruhrmann, Malin Almgren, Jesper N Tegnér, Tomas J Ekström, André Ortlieb Guerreiro-Cacais, Maja Jagodic
Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28194045/deregulation-of-regulatory-t-cells-in-acute-on-chronic-liver-failure-a-rat-model
#12
Shunlan Ni, Shanshan Li, Naibin Yang, Xinyue Tang, Shengguo Zhang, Danping Hu, Mingqin Lu
Aims. Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are similar in many respects during their acute exacerbation; however, ACLF generally has a poorer prognosis. We aimed to investigate the role and dynamic changes of regulatory T cell (Treg) and T helper 17 (Th17) cell proportions during ACLF progress. Methods. All rats were classified into two groups randomly: ACLF group and ALF group (control group). The rat model of ACLF was preestablished by intraperitoneal injection of carbon tetrachloride for 2 months...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28194020/cd103-lung-dendritic-cells-ldcs-induce-stronger-th1-th17-immunity-to-a-bacterial-lung-infection-than-cd11b-hi-ldcs
#13
Sudhanshu Shekhar, Ying Peng, Shuhe Wang, Xi Yang
Recent studies suggest differential roles for CD103+ and CD11b(hi) lung dendritic cells (LDCs) in host defense against viral and bacterial infections. In this study, we examined the contribution of these LDC subsets in protective immunity to chlamydial lung infection using a Chlamydia muridarum mouse infection model. We found that CD103+ LDCs showed higher expression of costimulatory molecules (CD40, CD80 and CD86) and increased production of cytokines (IL-12p70, IL-10, IL-23 and IL-6) compared with CD11b(hi) LDCs, but the expression of programmed death-ligand 1 (PD-L1) was similar between the two subsets...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28193225/the-active-metabolite-of-leflunomide-a77-1726-attenuates-inflammatory-arthritis-in-mice-with-spontaneous-arthritis-via-induction-of-heme-oxygenase-1
#14
Su-Jin Moon, Eun-Kyung Kim, Joo Yeon Jhun, Hee Jin Lee, Weon Sun Lee, Sang-Hi Park, Mi-La Cho, Jun-Ki Min
BACKGROUND: Leflunomide is a low-molecular-weight compound that is widely used in the treatment of rheumatoid arthritis. Although leflunomide is thought to act through the inhibition of the de novo pyrimidine synthesis, the molecular mechanism of the drug remains largely unknown. We investigated the antiarthritis effects and mechanisms of action of the active metabolite of leflunomide, A77 1726, in interleukin-1 receptor antagonist-knockout (IL-1Ra-KO) mice. METHODS: 14- to 15-week-old male IL-1Ra-KO mice were treated with 10 or 30 mg/kg A77 1726 via intraperitoneal injection three times per week for 6 weeks...
February 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28187441/neutralization-of-interleukin-9-ameliorates-symptoms-of-allergic-rhinitis-by-reducing-th2-th9-and-th17-responses-and-increasing-the-treg-response-in-a-murine-model
#15
Zhao Wei Gu, Yun Xiu Wang, Zhi Wei Cao
A novel independent Th-cell subset, characterized by high expression of interleukin (IL)-9, has been recognized as the "Th9" subset. Although Th9 cells are important in many diseases, their contribution to allergic rhinitis (AR) remains unclear. We therefore first determined whether Th9 cells were present in a mouse model of AR. We then investigated the their involvement in the distribution of CD4+ T-cell subsets and the symptoms of AR by treating mice with anti-IL-9 antibodies (Abs). Anti-IL-9 Abs were administered intranasally during rechallenge of ovalbumin (OVA)-induced AR in BALB/c mice...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186160/3-bromopyruvate-ameliorate-autoimmune-arthritis-by-modulating-th17-treg-cell-differentiation-and-suppressing-dendritic-cell-activation
#16
Takaichi Okano, Jun Saegusa, Keisuke Nishimura, Soshi Takahashi, Sho Sendo, Yo Ueda, Akio Morinobu
Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all isoforms of HK. Thus, it is unclear which isoform has a critical role in Th17 cell differentiation and in rheumatoid arthritis (RA) pathogenesis...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28183349/hif-1%C3%AE-inhibitor-echinomycin-reduces-acute-graft-versus-host-disease-and-preserves-graft-versus-leukemia-effect
#17
Yushi Yao, Lei Wang, Jihao Zhou, Xinyou Zhang
BACKGROUND: Acute graft-versus-host disease (aGVHD) remains a major obstacle against favorable clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T helper cells including Th17 play key roles in aGVHD pathogenesis. Donor regulatory T cell (Tregs) adoptive therapy reduces aGVHD without weakening graft-versus-leukemia effect (GVL) in both mouse and human, although the purification and ex vivo expansion of Tregs in clinical scenarios remain costly and technically demanding...
February 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28183330/th17-and-cd24-hi-cd27-regulatory-b-lymphocytes-are-biomarkers-of-response-to-biologics-in-rheumatoid-arthritis
#18
Sarah Salomon, Caroline Guignant, Pierre Morel, Gauthier Flahaut, Clément Brault, Clément Gourguechon, Patrice Fardellone, Jean-Pierre Marolleau, Brigitte Gubler, Vincent Goëb
BACKGROUND: The aim was to describe the regulatory B and T cells (Breg and Treg) and T helper 17 (Th17) lymphocytes before and under treatment with biologic drugs, and to assess their potential predictive value as biomarkers of response in rheumatoid arthritis (RA). METHODS: This was a non-randomised, single-centre, prospective study. Patients with active RA (American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010) who required the initiation or switch to any biologic drug except rituximab were included...
February 10, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28179509/iga-coated-e-coli-enriched-in-crohn-s-disease-spondyloarthritis-promote-th17-dependent-inflammation
#19
Monica Viladomiu, Charles Kivolowitz, Ahmed Abdulhamid, Belgin Dogan, Daniel Victorio, Jim G Castellanos, Viola Woo, Fei Teng, Nhan L Tran, Andrew Sczesnak, Christina Chai, Myunghoo Kim, Gretchen E Diehl, Nadim J Ajami, Joseph F Petrosino, Xi K Zhou, Sergio Schwartzman, Lisa A Mandl, Meira Abramowitz, Vinita Jacob, Brian Bosworth, Adam Steinlauf, Ellen J Scherl, Hsin-Jung Joyce Wu, Kenneth W Simpson, Randy S Longman
Peripheral spondyloarthritis (SpA) is a common extraintestinal manifestation in patients with active inflammatory bowel disease (IBD) characterized by inflammatory enthesitis, dactylitis, or synovitis of nonaxial joints. However, a mechanistic understanding of the link between intestinal inflammation and SpA has yet to emerge. We evaluated and functionally characterized the fecal microbiome of IBD patients with or without peripheral SpA. Coupling the sorting of immunoglobulin A (IgA)-coated microbiota with 16S ribosomal RNA-based analysis (IgA-seq) revealed a selective enrichment in IgA-coated Escherichia coli in patients with Crohn's disease-associated SpA (CD-SpA) compared to CD alone...
February 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28179433/il-36-signaling-facilitates-activation-of-the-nlrp3-inflammasome-and-il-23-il-17-axis-in-renal-inflammation-and-fibrosis
#20
Hsi-Hua Chi, Kuo-Feng Hua, Yu-Chuan Lin, Ching-Liang Chu, Chih-Yu Hsieh, Yu-Juei Hsu, Shuk-Man Ka, Yu-Ling Tsai, Feng-Cheng Liu, Ann Chen
IL-36 cytokines are proinflammatory and have an important role in innate and adaptive immunity, but the role of IL-36 signaling in renal tubulointerstitial lesions (TILs), a major prognostic feature of renal inflammation and fibrosis, remains undetermined. In this study, increased IL-36α expression detected in renal biopsy specimens and urine samples from patients with renal TILs correlated with renal function impairment. We confirmed the increased expression of IL-36α in the renal tubular epithelial cells of a mouse model of unilateral ureteral obstruction (UUO) and related cell models using mechanically induced pressure, oxidative stress, or high mobility group box 1...
February 8, 2017: Journal of the American Society of Nephrology: JASN
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