IL-22-Expressing Murine Lymphocytes Display Plasticity and Pathogenicity in Reporter Mice

Wei Shen, Julie A. Hixon, Mairi Hall McLean, Wen Qing Li, Scott K. Durum*

*Corresponding author for this work

Research output: Contribution to journalArticle

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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 IFN gamma 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.

Original languageEnglish
Article number662
Number of pages14
JournalFrontiers in Immunology
Volume6
DOIs
Publication statusPublished - 19 Jan 2016

Keywords

  • IL-22
  • Th17
  • Th22
  • T cell plasticity
  • IL-27
  • INNATE LYMPHOID-CELLS
  • CD4(+) T-CELLS
  • ROR-GAMMA-T
  • ARYL-HYDROCARBON RECEPTOR
  • FACTOR C-MAF
  • CUTTING EDGE
  • TH17 CELLS
  • INTESTINAL PATHOLOGY
  • IL-22 PRODUCTION
  • T(H)17 CELLS

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