title: IL-22-Expressing Murine Lymphocytes Display Plasticity and Pathogenicity in Reporter Mice.
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.
authors.affiliation: Cancer and Inflammation Program, Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, MD , USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: Cancer and Inflammation Program, Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, MD , USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Hixon
authors.affiliation: Cancer and Inflammation Program, Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, MD , USA.
authors.forename: Mairi H
authors.initials: MH
authors.lastname: McLean
authors.affiliation: Cancer and Inflammation Program, Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, MD , USA.
authors.forename: Wen Qing
authors.initials: WQ
authors.lastname: Li
authors.affiliation: Cancer and Inflammation Program, Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, MD , USA.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Durum
keywords: IL-22; IL-27; T cell plasticity; Th17; Th22
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