Interleukin (IL)-21 Promotes Intestinal IgA Responses to Microbiota

Cao AT, Yao S, Gong B, Nurieva RI, Elson CO, Cong Y.

Mucosal Immunol. 2015 Jan 14. doi: 10.1038/mi.2014.134.

Cong Photo

From Left to Right: Charles Elson, Anthony Cao and Yingzi Cong

The intestinal tract is colonized by trillions of commensal bacteria that live in a mutualistic relationship our bodies. Commensal microbiota-specific Th17 cells are enriched in the intestines and are crucial for production of intestinal IgA against microbiota; however, the role of Th17 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 IL-17 or IL-21 signaling. IL-21 is able to augment B-cell differentiation to IgA+ cells as mediated by TGFβ and accelerate IgA class switch recombination (CSR). Repletion of T-cell-deficient TCRβxδ-/- 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 α4β7 expression, alone or with TGFβ and retinoic acid. 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. PubMed:25586558