Yeste, AdaMascanfroni, Ivan D.Nadeau, MeghanBurns, Evan J.Tukpah, Ann-MarciaSantiago, AndrezzaWu, ChuanPatel, BonnyKumar, DeepakQuintana, Francisco2014-12-022014Yeste, Ada, Ivan D. Mascanfroni, Meghan Nadeau, Evan J. Burns, Ann-Marcia Tukpah, Andrezza Santiago, Chuan Wu, Bonny Patel, Deepak Kumar, and Francisco J. Quintana. 2014. “IL-21 induces IL-22 production in CD4+ T-cells.” Nature communications 5 (1): 3753. doi:10.1038/ncomms4753. http://dx.doi.org/10.1038/ncomms4753.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:13454814IL-22 produced by innate lymphoid cells (ILCs) and CD4+ T cells plays an important role in host defense and mucosal homeostasis, thus it is important to investigate the mechanisms that regulate IL-22 production. We investigated the regulation IL-22 production by CD4+ T cells. Here we show that IL-21 triggers IL-22, but not IL-17 production by CD4+ T cells. STAT3, activated by IL-21, controls the epigenetic status of the il22 promoter and its interaction with the aryl hydrocarbon receptor (AhR). Moreover, IL-21 and AhR signaling in T cells control IL-22 production and the development of dextran sodium sulfate-induced colitis in ILC-deficient mice. Thus, we have identified IL-21 as an inducer of IL-22 production in CD4+ T cells in vitro and in vivo.en-USJournal Article2014-12-0210.1038/ncomms4753