RRC ID |
55492
|
著者 |
Tang C, Kakuta S, Shimizu K, Kadoki M, Kamiya T, Shimazu T, Kubo S, Saijo S, Ishigame H, Nakae S, Iwakura Y.
|
タイトル |
Suppression of IL-17F, but not of IL-17A, provides protection against colitis by inducing Treg cells through modification of the intestinal microbiota.
|
ジャーナル |
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.
|
巻・号 |
19(7)
|
ページ |
755-765
|
公開日 |
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
|
引用数 |
47
|
リソース情報 |
一般微生物 |
JCM 12243
JCM 1291
JCM 12249
JCM 12083 |