Retinoic acid expression associates with enhanced IL-22 production by gammadelta T cells and innate lymphoid cells and attenuation of intestinal inflammation

Lisa A Mielke, Sarah A Jones, Mathilde Raverdeau, Rowan Higgs, Anna Stefanska, Joanna R Groom, Alicja Misiak, Lara Dungan, Caroline Sutton, Gundula Streubel, Adrian P Bracken, Kingston H G Mills

Research output: Contribution to journalArticleResearchpeer-review

183 Citations (Scopus)

Abstract

Retinoic acid (RA), a vitamin A metabolite, modulates mucosal T helper cell responses. Here we examined the role of RA in regulating IL-22 production by gammadelta T cells and innate lymphoid cells in intestinal inflammation. RA significantly enhanced IL-22 production by gammadelta T cells stimulated in vitro with IL-1beta or IL-18 and IL-23. In vivo RA attenuated colon inflammation induced by dextran sodium sulfate treatment or Citrobacter rodentium infection. This was associated with a significant increase in IL-22 secretion by gammadelta T cells and innate lymphoid cells. In addition, RA treatment enhanced production of the IL-22-responsive antimicrobial peptides Reg3beta and Reg3gamma in the colon. The attenuating effects of RA on colitis were reversed by treatment with an anti-IL-22 neutralizing antibody, demonstrating that RA mediates protection by enhancing IL-22 production. To define the molecular events involved, we used chromatin immunoprecipitation assays and found that RA promoted binding of RA receptor to the IL-22 promoter in gammadelta T cells. Our findings provide novel insights into the molecular events controlling IL-22 transcription and suggest that one key outcome of RA signaling may be to shape early intestinal immune responses by promoting IL-22 synthesis by gammadelta T cells and innate lymphoid cells.
Original languageEnglish
Pages (from-to)1117 - 1124
Number of pages5
JournalJournal of Experimental Medicine
Volume210
Issue number6
DOIs
Publication statusPublished - 2013
Externally publishedYes

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