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Naive and activated T cells display differential responsiveness to TL1A that affects Th17 generation, maintenance, and proliferation

Jones, Gareth Wyn, Stumhofer, Jason S., Foster, Tom, Twohig, Jason Peter, Hertzog, Paul, Topley, Nicholas, Williams, Anwen Sian, Hunter, Christopher A., Jenkins, Brendan J., Wang, Edward Chung Yern and Jones, Simon Arnett 2011. Naive and activated T cells display differential responsiveness to TL1A that affects Th17 generation, maintenance, and proliferation. The FASEB Journal 25 (1) , pp. 409-419. 10.1096/fj.10-166843

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Abstract

Tumor necrosis factor (TNF)-like cytokine (TL1A) is a T-cell costimulator that bolsters cytokine-induced activation through death receptor 3 (DR3). To explore the relationship between T-cell activation and TL1A responsiveness, flow cytometry profiled DR3 expression in resting and activated T cells. In human CD4+ T cells, DR3 was induced rapidly following activation and expressed prominently by interleukin (IL)-17-secreting T cells (Th17). Splenic T cells from wild-type and DR3-deficient mice showed that TL1A activation of DR3 inhibits Th17 generation (81±2.6% at 100 ng/ml TL1A) from naive T cells. This response was not associated with suppression of T-cell proliferation. Using neutralizing antibodies or T cells derived from genetically modified mice, TL1A inhibition of Th17 development was found to be independent of IL-2, IL-27, γIFN, IFNAR1, and STAT1. Under suboptimal TCR activation, TL1A continued to block IL-17A secretion, however, the reduced threshold of TCR engagement was now linked with an increase in TL1A-driven proliferation. In contrast, fully committed Th17 cells displayed an altered TL1A responsiveness and in the absence of TCR costimulation supported the maintenance of T cell IL-17A expression. Consequently, TL1A orchestrates unique outcomes in naive and effector T-helper cells, which may affect the proliferation, differentiation and maintenance of Th17 cells in peripheral compartments and inflamed tissues.—Jones, G. W., Stumhofer, J. S., Foster, T., Twohig, J.P., Hertzog, P., Topley, N., Williams, A. S., Hunter, C. A., Jenkins, B. J., Wang, E. C. Y., Jones, S. A. Naive and activated T cells display differential responsiveness to TL1A that affects Th17 generation, maintenance, and proliferation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > R Medicine (General)
Uncontrolled Keywords: Cytokine; T-cell regulation; Inflammation;
Publisher: Federation of American Society of Experimental Biology
ISSN: 0892-6638
Last Modified: 08 Oct 2018 21:21
URI: http://orca.cf.ac.uk/id/eprint/26418

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