Journal ArticleDOI
Suppression of IL-17F, but not of IL-17A, provides protection against colitis by inducing T reg cells through modification of the intestinal microbiota
Ce Tang,Shigeru Kakuta,Kenji Shimizu,Kenji Shimizu,Kenji Shimizu,Motohiko Kadoki,Motohiko Kadoki,Motohiko Kadoki,Tomonori Kamiya,Tomonori Kamiya,Tomonori Kamiya,Tomoyuki Shimazu,Tomoyuki Shimazu,Sachiko Kubo,Sachiko Kubo,Shinobu Saijo,Shinobu Saijo,Harumichi Ishigame,Susumu Nakae,Yoichiro Iwakura,Yoichiro Iwakura +20 more
TLDR
It is found that Il17f–/− mice resisted chemically induced colitis, but Il17a–/– mice did not, and that IL17f−/− CD45RBhiCD4+ T cells induced milder colitis in lymphocyte-deficient Rag2–/- mice, accompanied by an increase in intestinal regulatory T cells (Treg cells).Abstract:
The cytokines IL-17A and IL-17F have 50% amino-acid identity and bind the same receptor; however, their functional differences have remained obscure. Here we found that Il17f-/- mice resisted chemically induced colitis, but Il17a-/- mice did not, and that Il17f-/- CD45RBhiCD4+ T cells induced milder colitis in lymphocyte-deficient Rag2-/- mice, accompanied by an increase in intestinal regulatory T cells (Treg cells). Clostridium cluster XIVa in colonic microbiota capable of inducing Treg cells was increased in both Il17f-/- mice and mice given transfer Il17f-/- T cells, due to decreased expression of a group of antimicrobial proteins. There was substantial production of IL-17F, but not of IL-17A, not only by naive T cells but also by various colon-resident cells under physiological conditions. Furthermore, antibody to IL-17F suppressed the development of colitis, but antibody to IL-17A did not. These observations suggest that IL-17F is an effective target for the treatment of colitis.read more
Citations
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Journal ArticleDOI
Pathway paradigms revealed from the genetics of inflammatory bowel disease.
TL;DR: IBD is described as a model disease in the context of leveraging human genetics to dissect interactions in cellular and molecular pathways that regulate homeostasis of the mucosal immune system and future prospects for disease-subtype classification and therapeutic intervention are discussed.
Journal ArticleDOI
Mining the Microbiota for Microbial and Metabolite-Based Immunotherapies
TL;DR: How the intestinal microbiota profoundly shapes host physiology through its production of small molecules and metabolites is discussed, and the potential of ‘mining’ the microbiota for new microbial and metabolite-based immunotherapies is considered.
Journal ArticleDOI
TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions
Tianqi Leng,Hossain Delowar Akther,Hackstein C-P.,Kate Powell,Thomas C. King,Matthias Friedrich,Zoe Christoforidou,Sarah McCuaig,Mastura Neyazi,Carolina V. Arancibia-Cárcamo,Joachim Hagel,Fiona Powrie,Raphael S. Peres,Val Millar,Daniel Ebner,Rajesh Lamichhane,James E. Ussher,Hinks Tsc.,Emanuele Marchi,Christian B. Willberg,Paul Klenerman,Paul Klenerman +21 more
TL;DR: Data indicate the blend of T CR-dependent and TCR-independent signaling to CD8+ MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair.
Journal ArticleDOI
Microbiome Dependent Regulation of Tregs and Th17 Cells in Mucosa.
Pushpa Pandiyan,Natarajan Bhaskaran,Mangge Zou,Elizabeth Schneider,Sangeetha Jayaraman,Jochen Huehn +5 more
TL;DR: Mechanisms by which commensal microbes influence mucosa in the context of bioactive molecules derived from resident bacteria, immune senescence, chronic inflammation and cancer are reviewed.
Journal ArticleDOI
Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption.
Hideki Kitaura,Aseel Marahleh,Fumitoshi Ohori,Takahiro Noguchi,Wei Ren Shen,Jiawei Qi,Yasuhiko Nara,Adya Pramusita,Ria Kinjo,Itaru Mizoguchi +9 more
TL;DR: Findings suggest that osteocyte-related cytokines act directly to enhance osteoclast formation and bone resorption, and discuss the osteocyte as the master regulator of bone Resorption and effector in osteoc last formation.
References
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Journal ArticleDOI
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Yukihiro Furusawa,Yuuki Obata,Shinji Fukuda,Takaho A. Endo,Gaku Nakato,Daisuke Takahashi,Yumiko Nakanishi,Chikako Uetake,Keiko Kato,Tamotsu Kato,Masumi Takahashi,Noriko N. Fukuda,Shinnosuke Murakami,Eiji Miyauchi,Shingo Hino,Koji Atarashi,Satoshi Onawa,Yumiko Fujimura,Trevor Lockett,Julie M. Clarke,David L. Topping,Masaru Tomita,Shohei Hori,Osamu Ohara,Tatsuya Morita,Haruhiko Koseki,Jun Kikuchi,Kenya Honda,Koji Hase,Hiroshi Ohno +29 more
TL;DR: It is shown that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice and ameliorated the development of colitis induced by adoptive transfer of CD4+ CD45RBhi T cells in Rag1−/− mice.
Journal ArticleDOI
Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species
Koji Atarashi,Takeshi Tanoue,Tatsuichiro Shima,Akemi Imaoka,Tomomi Kuwahara,Yoshika Momose,Genhong Cheng,Sho Yamasaki,Takashi Saito,Yusuke Ohba,Tadatsugu Taniguchi,Kiyoshi Takeda,Shohei Hori,Ivaylo I. Ivanov,Yoshinori Umesaki,Kikuji Itoh,Kenya Honda,Kenya Honda +17 more
TL;DR: Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.
Journal ArticleDOI
Differentiation of Effector CD4 T Cell Populations
TL;DR: This review summarizes the discovery, functions, and relationships among Th cells; the cytokine and signaling requirements for their development; the networks of transcription factors involved in their differentiation; the epigenetic regulation of their key cytokines and transcription factors; and human diseases involving defective CD4 T cell differentiation.
Journal ArticleDOI
Clinicopathologic study of dextran sulfate sodium experimental murine colitis
TL;DR: The finding of crypt loss without proceeding or accompanying inflammation suggests that the initial insult is at the level of the epithelial cell with inflammation being a secondary phenomena.
Journal ArticleDOI
NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis
Eran Elinav,Till Strowig,Andrew L. Kau,Jorge Henao-Mejia,Christoph A. Thaiss,Carmen J. Booth,David R. Peaper,John Bertin,Stephanie C. Eisenbarth,Jeffrey I. Gordon,Richard A. Flavell,Richard A. Flavell +11 more
TL;DR: It is shown that deficiency of NLRP6 in mouse colonic epithelial cells results in reduced IL-18 levels and altered fecal microbiota characterized by expanded representation of the bacterial phyla Bacteroidetes (Prevotellaceae) and TM7.
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