@ARTICLE{10.3389/fimmu.2015.00662, AUTHOR={Shen, Wei and Hixon, Julie A. and McLean, Mairi H. and Li, Wen Qing and Durum, Scott K.}, TITLE={IL-22-Expressing Murine Lymphocytes Display Plasticity and Pathogenicity in Reporter Mice}, JOURNAL={Frontiers in Immunology}, VOLUME={6}, YEAR={2016}, URL={https://www.frontiersin.org/articles/10.3389/fimmu.2015.00662}, DOI={10.3389/fimmu.2015.00662}, ISSN={1664-3224}, ABSTRACT={IL-22 has multiple activities ranging from tissue repair to inflammation. To characterize the pathogenicity and plasticity of cells that produce IL-22, a novel reporter mouse strain was generated. Homeostatic IL-22 reporter expression was observed in intestinal lymphoid cells identified as CD4 T cells and ILC3 cells. In a model of inflammatory bowel disease, CD4 T cells strongly expressed the IL-22 reporter in mesenteric lymph node. To examine plasticity of IL-22+ T cells, they were purified after generation in vitro or in vivo from inflamed colon, and then cultured under Th1, Th2, or Th17 conditions. In vitro-generated IL-22+ CD4 T cells showed relatively durable IL-22 expression under Th1 or Th2 conditions, whereas in vivo-generated cells rapidly lost IL-22 expression under these conditions. In vitro-generated cells could not be diverted to express Th1 or Th2 cytokines despite the expression of “master regulators.” In vivo-generated cells could be diverted, at very low frequency, to express Th1 or Th2 cytokines. Both in vitro- and in vivo-generated cells could be induced in vitro to express high levels of IL-17A and IL-17F, assigning them to a “Th17 biased” class. However, IL-27 potently downregulated IL-22 expression. To examine IL-22+ T cell pathogenicity, in vitro-generated cells were transferred into Rag1−/− mice, retaining the modest reporter expression and inducing moderate colitis. In contrast, IL-22 expressers from colitic mice, transferred into secondary hosts, lost reporter expression, acquired high T-bet and modest IFNγ and IL-17 expression, and induced severe colitis. These findings are consistent with a model of strong polarization under optimal in vitro conditions, but a plastic state of T cells in vivo.} }