| First Author | Mielke LA | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 6 | Pages | 1117-24 |
| PubMed ID | 23690441 | Mgi Jnum | J:201007 |
| Mgi Id | MGI:5510632 | Doi | 10.1084/jem.20121588 |
| Citation | Mielke LA, et al. (2013) Retinoic acid expression associates with enhanced IL-22 production by gammadelta T cells and innate lymphoid cells and attenuation of intestinal inflammation. J Exp Med 210(6):1117-24 |
| abstractText | 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. |
