Cutting edge: ICOS-deficient regulatory T cells display normal induction of IL10 but readily downregulate expression of Foxp3

Academic Article

Abstract

  • Copyright © 2019 by The American Association of Immunologists, Inc. The ICOS pathway has been implicated in the development and functions of regulatory T (Treg) cells, including those producing IL-10. Treg cell–derived IL-10 is indispensable for the establishment and maintenance of intestinal immune homeostasis. We examined the possible involvement of the ICOS pathway in the accumulation of murine colonic Foxp3- and/or IL-10–expressing cells. We show that ICOS deficiency does not impair induction of IL-10 by intestinal CD4 T cells but, instead, triggers substantial reductions in gut-resident and peripherally derived Foxp3 + Treg cells. ICOS deficiency is associated with reduced demethylation of Foxp3 CNS2 and enhanced loss of Foxp3. This instability significantly limits the ability of ICOS-deficient Treg cells to reverse ongoing inflammation. Collectively, our results identify a novel role for ICOS costimulation in imprinting the functional stability of Foxp3 that is required for the retention of full Treg cell function in the periphery.
  • Digital Object Identifier (doi)

    Author List

  • Landuyt AE; Klocke BJ; Colvin TB; Schoeb TR; Maynard CL
  • Start Page

  • 1039
  • End Page

  • 1044
  • Volume

  • 202
  • Issue

  • 4