| First Author | Cao AT | Year | 2015 |
| Journal | Mucosal Immunol | Volume | 8 |
| Issue | 5 | Pages | 1072-82 |
| PubMed ID | 25586558 | Mgi Jnum | J:338005 |
| Mgi Id | MGI:6837566 | Doi | 10.1038/mi.2014.134 |
| Citation | Cao AT, et al. (2015) Interleukin (IL)-21 promotes intestinal IgA response to microbiota. Mucosal Immunol 8(5):1072-82 |
| abstractText | Commensal microbiota-specific T helper type 17 (Th17) cells are enriched in the intestines, which can convert into T follicular helper (Tfh) in Peyer's patches, and are crucial for production of intestinal immunoglobulin A (IgA) against microbiota; however, the role of Th17 and Tfh cytokines in regulating the mucosal IgA response to enteric microbiota is still not completely known. In this study, we found that intestinal IgA was impaired in mice deficient in interleukin (IL)-17 or IL-21 signaling. IL-21, but not IL-17, is able to augment B-cell differentiation to IgA(+) cells as mediated by transforming growth factor beta1 (TGFbeta1) and accelerate IgA class switch recombination (CSR). IL-21 and retinoic acid (RA) induce IgA(+) B-cell development and IgA production and drives autocrine TGFbeta1 production to initiate IgA CSR. Repletion of T-cell-deficient TCRbetaxdelta(-/-) mice with Th17 cells specific for commensal bacterial antigen increased the levels of IgA(+) B cells and IgA production in the intestine, which was blocked by neutralizing IL-21. Thus IL-21 functions to strongly augment IgA production under intestinal environment. Furthermore, IL-21 promotes intestinal B-cell homing through alpha4beta7 expression, alone or with TGFbeta and RA. Together, IL-21 from microbiota-specific Th17 and/or Tfh cells contributes to robust intestinal IgA levels by enhancing IgA(+) CSR, IgA production and B-cell trafficking into the intestine. |
