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Craig Maynard, Casey Weaver, Role of the ICOS-ICOSL pathway in development and function of intestinal regulatory T cells: P-192., Inflammatory Bowel Diseases, Volume 17, Issue Suppl_2, 1 December 2011, Page S70, https://doi.org/10.1097/00054725-201112002-00226
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The inducible co-stimulator (ICOS) is a CD28 homologue that is upregulated on T cells subsequent to TCR activation. Co-stimulation of T cells through the interaction of ICOS with the ICOS ligand (ICOSL; also referred to as B7h, B7RP-1, GL-50, and B7-H2) on antigen-presenting cells results in the modulation of effector T cell responses. Importantly, ICOSL has been identified by genome-wide association studies as a susceptibility allele for IBD consistent with high expression of ICOSL on B cells, macrophages, and epithelial cells in the intestinal mucosa of IBD patients. The ICOS-ICOSL pathway has also been implicated in development and function of regulatory T cells (Treg cells), particularly antigen-induced, IL-10-producing Treg that develop in vivo and in vitro. Thus, one possible explanation for the association of the ICOS-ICOSL pathway with increased risk of IBD is defective development and/or function of ICOS-dependent IL-10-producing Treg cells. Considering the importance of this Treg cell subset in intestinal immune regulation, we investigated the role of the ICOS-ICOSL pathway in their development and function in vivo. We found that IL-10 can be induced in CD4 T cells in vivo in the absence of ICOS signaling and that previous expression of ICOS is not required for the development of IL-10 competency, or maintenance of immune homeostasis by intestinal Treg cells. Instead, co-stimulation via ICOS stimulates high-level secretion of IL-10 by Treg cells ex vivo. Collectively, our data demonstrate that ICOS dispensable for intestinal Treg cell development but suggests that its expression on a subset of in vivo Treg cells facilitates elevated expression of IL-10 that may be serve to enhance the threshold for development and/or maintenance of intestinal inflammation.
- alleles
- signal transduction
- inflammation
- b-lymphocytes
- inflammatory bowel disease
- homeostasis
- antigen-presenting cells
- antigens
- cd28 antigens
- bodily secretions
- interleukin-10
- intestinal mucosa
- intestines
- ligands
- macrophages
- t-lymphocytes
- helper-inducer t-lymphocytes
- irritable bowel syndrome
- epithelial cells
- regulatory t-lymphocytes
- genome-wide association study
- lymphocyte costimulation
