Interleukin (IL)-21 promotes intestinal IgA response to microbiota

A. T. Cao, Suxia Yao, Bin Gong, R. I. Nurieva, C. O. Elson, Yingzi Cong

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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 β1 (TGFβ1) and accelerate IgA class switch recombination (CSR). IL-21 and retinoic acid (RA) induce IgA + B-cell development and IgA production and drives autocrine TGFβ1 production to initiate IgA 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 4 β 7 expression, alone or with TGFβ 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.

Original languageEnglish (US)
Pages (from-to)1072-1082
Number of pages11
JournalMucosal Immunology
Volume8
Issue number5
DOIs
StatePublished - Sep 19 2015

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Microbiota
Immunoglobulin A
B-Lymphocytes
Immunoglobulin Isotypes
Genetic Recombination
Intestines
Th17 Cells
Interleukin-17
Transforming Growth Factors
Tretinoin
interleukin-21
Bacterial Antigens
Peyer's Patches
Helper-Inducer T-Lymphocytes
Cell Differentiation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Interleukin (IL)-21 promotes intestinal IgA response to microbiota. / Cao, A. T.; Yao, Suxia; Gong, Bin; Nurieva, R. I.; Elson, C. O.; Cong, Yingzi.

In: Mucosal Immunology, Vol. 8, No. 5, 19.09.2015, p. 1072-1082.

Research output: Contribution to journalArticle

Cao, A. T. ; Yao, Suxia ; Gong, Bin ; Nurieva, R. I. ; Elson, C. O. ; Cong, Yingzi. / Interleukin (IL)-21 promotes intestinal IgA response to microbiota. In: Mucosal Immunology. 2015 ; Vol. 8, No. 5. pp. 1072-1082.
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