RRC ID 55492
Author Tang C, Kakuta S, Shimizu K, Kadoki M, Kamiya T, Shimazu T, Kubo S, Saijo S, Ishigame H, Nakae S, Iwakura Y.
Title Suppression of IL-17F, but not of IL-17A, provides protection against colitis by inducing Treg cells through modification of the intestinal microbiota.
Journal Nat Immunol
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.
Volume 19(7)
Pages 755-765
Published 2018-7-1
DOI 10.1038/s41590-018-0134-y
PII 10.1038/s41590-018-0134-y
PMID 29915298
MeSH Animals Cells, Cultured Clostridium / growth & development Clostridium / isolation & purification Colitis / drug therapy Colitis / immunology* Gastrointestinal Microbiome* Interleukin-17 / antagonists & inhibitors* Interleukin-17 / genetics Interleukin-17 / physiology Intestines / immunology Mice Mice, Inbred C57BL Mice, Knockout Phospholipases A2 / biosynthesis Phospholipases A2 / genetics Prevotella / isolation & purification Ribonuclease, Pancreatic / biosynthesis Ribonuclease, Pancreatic / genetics T-Lymphocytes, Regulatory / immunology* beta-Defensins / biosynthesis
IF 23.53
Times Cited 47
General Microbes JCM 12243 JCM 1291 JCM 12249 JCM 12083