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

Mielke, LA; Jones, SA; Raverdeau, M; Higgs, R; Stefanska, A; Groom, JR; Misiak, A; Dungan, LS; Sutton, CE; Streubel, G; Bracken, AP; Mills, KHG

Author(s): Mielke, LA; Jones, SA; Raverdeau, M; Higgs, R; Stefanska, A; Groom, JR; Misiak, A; Dungan, LS; Sutton, CE; Streubel, G; Bracken, AP; Mills, KHG;
Details: Publication Year 2013-06-03,Volume 210,Issue #6,Page 1117-1124
Journal Title: JOURNAL OF EXPERIMENTAL MEDICINE
Publication Type: Journal Article
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 gamma delta T cells and innate lymphoid cells in intestinal inflammation. RA significantly enhanced IL-22 production by gamma delta T cells stimulated in vitro with IL-1 beta 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 gamma delta T cells and innate lymphoid cells. In addition, RA treatment enhanced production of the IL-22-responsive antimicrobial peptides Reg3 beta and Reg3 gamma 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 gamma delta 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 gamma delta T cells and innate lymphoid cells.
Publisher: ROCKEFELLER UNIV PRESS
Keywords: DENDRITIC CELLS; BOWEL-DISEASE; IMMUNITY; INTERLEUKIN-22; GENERATION; PROTECTION; MECHANISM; RESPONSES
Research Division(s): Molecular Immunology
Link To PubMed Central Version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674702/
Publisher's Version: https://doi.org/10.1084/jem.20121588
Open Access at Publisher's Site: http://jem.rupress.org/content/210/6/1117.long
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Creation Date: 2013-06-03 12:00:00