Th17 cells upregulate polymeric Ig receptor and intestinal IgA and contribute to intestinal homeostasis

Anthony T. Cao, Suxia Yao, Bin Gong, Charles O. Elson, Yingzi Cong

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

Although CD4+ Th17 cells are enriched in normal intestines, their role in regulation of the host response to microbiota, and whether and how they contribute to intestinal homeostasis, is still largely unknown. It is also unclear whether Th17 cells regulate intestinal IgA production, which is also abundant in the intestinal lumen and has a crucial role as the first defense line in host response to microbiota. In this study, we found that intestinal polymeric Ig receptor (pIgR) and IgA production was impaired in T cell-deficient TCR-βxδ-/- mice. Repletion of TCR-βxδ -/- mice with Th17 cells from CBir1 flagellin TCR transgenic mice, which are specific for a commensal Ag, increased intestinal pIgR and IgA. The levels of intestinal pIgR and IgA in B6.IL-17R (IL-17R-/-) mice were lower than wild type mice. Treatment of colonic epithelial HT-29 cells with IL-17 increased pIgR expression. IL-17R-/- mice demonstrated systemic antimicroflora Ab response. Consistently, administering dextran sulfate sodium (DSS) to C57BL/6 mice after treatment with IL-17-neutralizing Ab resulted in more severe intestinal inflammation compared with control Ab. Administering DSS to IL-17R-/- mice resulted in increased weight loss and more severe intestinal inflammation compared with wild type mice, indicating a protective role of Th17 cells in intestinal inflammation. Individual mice with lower levels of pIgR and intestinal-secreted IgA correlated with increased weight loss at the end of DSS administration. Collectively, our data reveal that microbiota-specific Th17 cells contribute to intestinal homeostasis by regulating intestinal pIgR expression and IgA secretion.

Original languageEnglish (US)
Pages (from-to)4666-4673
Number of pages8
JournalJournal of Immunology
Volume189
Issue number9
DOIs
StatePublished - Nov 1 2012

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ASJC Scopus subject areas

  • Immunology

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