title: Interleukin (IL)-21 promotes intestinal IgA response to microbiota.
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 α4β7 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.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Cao
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: B
authors.initials: B
authors.lastname: Gong
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA.
authors.forename: R I
authors.initials: RI
authors.lastname: Nurieva
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: C O
authors.initials: CO
authors.lastname: Elson
authors.affiliation: 1] Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA [2] Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Cong
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D018928:Immunity, Mucosal / Q000502:physiology*; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D007070:Immunoglobulin A; D020381:Interleukin-17; D007378:Interleukins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D000098546:Interleukin-21