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Role of theICOS-ICOSL pathway indevelopment andfunction ofintestinal regulatoryT cells Craig L. MaynardCasey T. Weaver2011 год

Role of the ICOS-ICOSL pathway in development and function of intestinal regulatory T cells
статья из журнала

Страница публикацииПубликация в OpenAlex
Аннотация: 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.
Год издания: 2011
Авторы: Craig L. Maynard, Casey T. Weaver
Издательство: Oxford University Press
Источник: Inflammatory Bowel Diseases
Ключевые слова: T-cell and B-cell Immunology, Immune Cell Function and Interaction, Atherosclerosis and Cardiovascular Diseases