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Aryl hydrocarbon receptor AND TH17 AND treg

Iain A Murray, Robert G Nichols, Limin Zhang, Andrew D Patterson, Gary H Perdew
Environmental and genetic factors represent key components in the establishment/maintenance of the intestinal microbiota. The aryl hydrocarbon receptor (AHR) is emerging as a pleiotropic factor, modulating pathways beyond its established role as a xenobiotic sensor. The AHR is known to regulate immune surveillance within the intestine through retention of intraepithelial lymphocytes, functional redistribution of Th17/Treg balance. Consequently, environmental/genetic manipulation of AHR activity likely influences host-microbe homeostasis...
September 23, 2016: Scientific Reports
Bei Tong, Xusheng Yuan, Yannong Dou, Xin Wu, Yuhui Wang, Yufeng Xia, Yue Dai
Sinomenine (SIN), an anti-arthritis drug, has previously been proven to exert immunomodulatory activity in rats by inducing intestinal regulatory T-cells (Treg cells). Here, we assessed the effect of SIN on the generation and function of Treg cells in autoimmune arthritis, and the underlying mechanisms in view of aryl hydrocarbon receptor (AhR). The proportions of Treg cells and IL-17-producing T-cells (Th17 cells) differentiated from naive T-cells were analyzed by flow cytometric analysis. The AhR agonistic effect of SIN was tested by analyzing the activation of downstream signaling pathways and target genes...
October 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Bei Tong, Xusheng Yuan, Yannong Dou, Xin Wu, Guixin Chou, Zhengtao Wang, Yufeng Xia, Yue Dai
OBJECTIVE: Norisoboldine (NOR), an isoquinoline alkaloid with very poor oral bioavailability, was previously proven to have a unique anti-arthritis activity in rats by inducing intestinal Treg cells. Herein, we explored its underlying mechanism in view of aryl hydrocarbon receptor (AhR). METHODS: The differentiation of regulatory T cells (Treg cells) and IL-17-producing T cells (Th17 cells) from naïve T cells was analyzed in vitro. The key role of AhR was ascertained using siRNA transfection...
June 2016: International Journal of Biochemistry & Cell Biology
Xiao-ming Li, Juan Peng, Wen Gu, Xue-jun Guo
The aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, has recently been demonstrated to regulate T cell differentiation. Whether AhR activation participates in allergic airway inflammation remains unknown. In the current study, using a non-eosinophilic asthma model, we demonstrate that 2, 3, 7, 8-tetrachlorodibenzo-P-dioxin (TCDD), a potent AhR ligand, reduced the airway infiltration of neutrophils, airway hyperresponsiveness and Th17 cytokine expression. Furthermore, stimulation with TCDD promoted Treg differentiation and inhibited Th17 differentiation...
2016: PloS One
Eun-Ju Yang, John V Stokes, Evangel Kummari, Jeffrey Eells, Barbara L F Kaplan
Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder, characterized by demyelination of neurons in the central nervous system. To investigate the pathogenicity of various T cell types in MS, especially IFN-γ- or IL-17-producing CD4(+ )cells (TH1 or TH17 cells, respectively), the mouse model, experimental autoimmune encephalomyelitis (EAE), is commonly used. One method by which EAE is induced is immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (MOG35-55) followed by subsequent injections of pertussis toxin (PTX) as an adjuvant...
May 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Narendra P Singh, Udai P Singh, Michael Rouse, Jiajia Zhang, Saurabh Chatterjee, Prakash S Nagarkatti, Mitzi Nagarkatti
Aryl hydrocarbon receptor (AhR) has been shown to have profound influence on T cell differentiation, and use of distinct AhR ligands has shown that whereas some ligands induce regulatory T cells (Tregs), others induce Th17 cells. In the present study, we tested the ability of dietary AhR ligands (indole-3-carbinol [I3C] and 3,3'-diindolylmethane [DIM]) and an endogenous AhR ligand, 6-formylindolo(3,2-b)carbazole (FICZ), on the differentiation and functions of Tregs and Th17 cells. Treatment of C57BL/6 mice with indoles (I3C or DIM) attenuated delayed-type hypersensitivity (DTH) response to methylated BSA and generation of Th17 cells while promoting Tregs...
February 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Xusheng Yuan, Bei Tong, Yannong Dou, Xin Wu, Zhifeng Wei, Yue Dai
Tetrandrine is an alkaloid constituent of the root of Stephania tetrandra S. Moore. The long-term clinical uses of tetrandrine for treatments of rheumatalgia and arthralgia as well as the inhibition of rat adjuvant-induced arthritis imply that tetrandrine may have therapeutic potential in rheumatoid arthritis (RA). Here, we explored its anti-RA mechanism in collagen-induced arthritis (CIA) in relation to the balance between T helper (Th) 17 cells and regulatory T (Treg) cells. DBA/1 mice were immunized with chicken type II collagen and were orally administered tetrandrine for 14 consecutive days...
February 1, 2016: Biochemical Pharmacology
Allison K Ehrlich, Jamie M Pennington, Xisheng Wang, Diana Rohlman, Sumit Punj, Christiane V Löhr, Matthew T Newman, Siva K Kolluri, Nancy I Kerkvliet
Aryl hydrocarbon receptor (AhR) activation by high-affinity ligands mediates immunosuppression in association with increased regulatory T cells (Tregs), making this transcription factor an attractive therapeutic target for autoimmune diseases. We recently discovered 10-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ), a nanomolar affinity AhR ligand with immunosuppressive activity and favorable pharmacologic properties. In this study, we tested the consequences of AhR activation in the NOD model...
January 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
S M Bellemore, E Nikoopour, J A Schwartz, O Krougly, E Lee-Chan, B Singh
T helper type 17 (Th17) cells have been shown to be pathogenic in autoimmune diseases; however, their role in type 1 diabetes (T1D) remains inconclusive. We have found that Th17 differentiation of CD4(+) T cells from BDC2·5 T cell receptor transgenic non-obese diabetic (NOD) mice can be driven by interleukin (IL)-23+IL-6 to produce large amounts of IL-22, and these cells induce T1D in young NOD mice upon adoptive transfer. Conversely, polarizing these cells with transforming growth factor (TGF)-β+IL-6 led to non-diabetogenic regulatory Th17 (Treg 17) cells that express high levels of aryl hydrocarbon receptor (AhR) and IL-10 but produced much reduced levels of IL-22...
December 2015: Clinical and Experimental Immunology
Sonia Mohinta, Arun K Kannan, Krishne Gowda, Shantu G Amin, Gary H Perdew, Avery August
The aryl hydrocarbon receptor (AHR) is regarded as an environmental sensor and has been shown to link environmental stresses with chronic inflammatory and autoimmune diseases. The AHR can be activated to regulate both the X/DRE (xenobiotic or dioxin response elements) as well as a non-X/DRE mediated pathway. Selective AHR modulators (SAhRMs) are recently identified compounds that activate non-X/DRE mediated pathway without activating the X/DRE-driven responses. Here, we have used 3 classes of AHR ligands; agonist, antagonist, and a SAhRM, to delineate the role of these AHR-driven pathways in T helper 17 (Th17)/T regulatory (Treg) regulation...
June 2015: Toxicological Sciences: An Official Journal of the Society of Toxicology
Yun Liu, Weimin She, Fuping Wang, Jing Li, Jiyao Wang, Wei Jiang
This study was designed to discuss the effects of 3, 3'-diindolylmethane (DIM) on methionine-choline-deficient (MCD)-diet induced mouse nonalcoholic steatohepatitis (NASH) and the potential mechanisms. NASH mice were administrated with or without DIM at different concentrations for 8 weeks. Both the in-vivo and in-vitro effects of DIM on Treg/Th17 imbalance during NASH progression were analyzed. The in-vivo blocking of CD25 or IL-17 was performed to respectively deplete respective function of Treg or Th17 subset...
December 2014: International Immunopharmacology
Jennifer J Heller, Hilde Schjerven, Shiyang Li, Aileen Lee, Ju Qiu, Zong-Ming E Chen, Stephen T Smale, Liang Zhou
Proper immune responses are needed to control pathogen infection at mucosal surfaces. IL-22-producing CD4(+) T cells play an important role in controlling bacterial infection in the gut; however, transcriptional regulation of these cells remains elusive. In this study, we show that mice with targeted deletion of the fourth DNA-binding zinc finger of the transcription factor Ikaros had increased IL-22-producing, but not IL-17-producing, CD4(+) T cells in the gut. Adoptive transfer of CD4(+) T cells from these Ikaros-mutant mice conferred enhanced mucosal immunity against Citrobacter rodentium infection...
October 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Michaela Gasch, Tina Goroll, Mario Bauer, Denise Hinz, Nicole Schütze, Tobias Polte, Dörthe Kesper, Jan C Simon, Jörg Hackermüller, Irina Lehmann, Gunda Herberth
The T helper cell subsets Th1, Th2, Th17, and Treg play an important role in immune cell homeostasis, in host defense, and in immunological disorders. Recently, much attention has been paid to Th17 cells which seem to play an important role in the early phase of the adoptive immune response and autoimmune disease. When generating Th17 cells under in vitro conditions the amount of IL-17A producing cells hardly exceeds 20% while the nature of the remaining T cells is poorly characterized. As engagement of the aryl hydrocarbon receptor (AHR) has also been postulated to modulate the differentiation of T helper cells into Th17 cells with regard to the IL-17A expression we ask how far do Th17 polarizing conditions in combination with ligand induced AHR activation have an effect on the production of other T helper cell cytokines...
2014: Mediators of Inflammation
Margaret M Lowe, Jeff E Mold, Bittoo Kanwar, Yong Huang, Alexander Louie, Michael P Pollastri, Cuihua Wang, Gautam Patel, Diana G Franks, Jennifer Schlezinger, David H Sherr, Allen E Silverstone, Mark E Hahn, Joseph M McCune
The aryl hydrocarbon receptor (AHR) binds to environmental toxicants including synthetic halogenated aromatic hydrocarbons and is involved in a diverse array of biological processes. Recently, the AHR was shown to control host immunity by affecting the balance between inflammatory T cells that produce IL-17 (Th17) and IL-22 versus regulatory T cells (Treg) involved in tolerance. While environmental AHR ligands can mediate this effect, endogenous ligands are likely to be more relevant in host immune responses...
2014: PloS One
João H Duarte, Paola Di Meglio, Keiji Hirota, Helena Ahlfors, Brigitta Stockinger
The aryl hydrocarbon receptor (AhR) has been attributed with anti-inflammatory effects in the development of pathological immune responses leading to experimental autoimmune encephalomyelitis (EAE) via the induction of regulatory T cells. In agreement with previously published findings, we find that TCDD administration confers protection from EAE, however, this immuno-modulatory effect was not the consequence of de novo Treg generation, but the inhibition of Th17 cell differentiation. Systemic application of FICZ at the time of immunization also reduced EAE pathology albeit to a lesser degree than TCDD...
2013: PloS One
Nan Hao, Murray L Whitelaw
The aryl hydrocarbon receptor (AhR) is traditionally defined as a transcriptional regulator involved in adaptive xenobiotic response, however, emerging evidence supports physiological functions of AhR in normal cell development and immune response. The role of AhR in immunomodulation is multi-dimensional. On the one hand, activation of AhR by TCDD and other ligands leads to profound immunosuppression, potentially via skewed Th1/Th2 cell balance toward Th1 dominance, and boosted Treg cell differentiation. On the other hand, activation of AhR can also induce Th17 cell polarization and increase the severity of autoimmune disease...
September 1, 2013: Biochemical Pharmacology
Philip B Busbee, Michael Rouse, Mitzi Nagarkatti, Prakash S Nagarkatti
The aim of this review is to discuss research involving ligands for the aryl hydrocarbon receptor (AhR) and their role in immunomodulation. While activation of the AhR is well known for its ability to regulate the biochemical and toxic effects of environmental chemicals, more recently an exciting discovery has been made indicating that AhR ligation can also regulate T-cell differentiation, specifically through activation of Foxp3(+) regulatory T cells (Tregs) and downregulation of the proinflammatory Th17 cells...
June 2013: Nutrition Reviews
Zhen Huang, Yucui Jiang, Yang Yang, Juan Shao, Xulun Sun, Jiangning Chen, Lei Dong, Junfeng Zhang
The T cell is pivotal in orchestrating and promoting an immune response during ulcerative colitis (UC). The aryl hydrocarbon receptor (AhR) is involved in the regulation of T cell responses, and 3,3'-diindolylmethane (DIM) is a known ligand of AhR. The aim of this study was to examine the therapeutic effects of DIM in experimental colitis and to investigate the possible mechanisms underlying its effects on mucosal T cell responses. The therapeutic effects of DIM were studied in an oxazolone-induced colitis model...
April 2013: Molecular Immunology
Diana Rohlman, Duy Pham, Zhen Yu, Linda B Steppan, Nancy I Kerkvliet
Activation of the aryl hydrocarbon receptor (AhR) by its prototypic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mediates potent suppression of T-cell dependent immune responses. The suppressive effects of TCDD occur early during CD4(+) T-cell differentiation in the absence of effects on proliferation and have recently been associated with the induction of AhR-dependent regulatory T-cells (Treg). Since AhR functions as a ligand-activated transcription factor, changes in gene expression induced by TCDD during the early stages of CD4(+) T-cell differentiation are likely to reflect fundamental mechanisms of AhR action...
2012: Frontiers in Immunology
Takayuki Yoshida, Ken Katsuya, Takahiro Oka, Shin-ichi Koizumi, Daiko Wakita, Hidemitsu Kitamura, Takashi Nishimura
The aryl hydrocarbon receptor (AhR) has been shown to play important roles in the immune system, and contributions of AhR ligands to the differentiation and functions of Th17/Treg cells have recently been established. However, it has not been fully clarified whether AhR plays roles in B cell differentiation and functions. The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly potent AhR agonist, was reported to suppress the production of immunoglobulin M (IgM) in a transformed mouse B cell line...
April 2012: Biomedical Research
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