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Loss of CD4+ T Cell IL-6R expression during inflammation underlines a role for IL-6 trans signaling in the local maintenance of Th17 cells

Jones, Gareth Wyn, McLoughlin, Rachel Mary, Hammond, Victoria Jayne, Parker, Clare Rhian, Williams, John, Malhotra, Raj, Scheller, Jurgen, Williams, Anwen, Rose-John, Stefan, Topley, Nicholas and Jones, Simon Arnett 2010. Loss of CD4+ T Cell IL-6R expression during inflammation underlines a role for IL-6 trans signaling in the local maintenance of Th17 cells. The Journal of Immunology 184 (4) , pp. 2130-2139. 10.4049/jimmunol.0901528

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Abstract

IL-6 responses are classically orchestrated via a membrane-bound IL-6R (CD126) α subunit (classical IL-6R signaling) or through a soluble form of this cognate receptor (IL-6 trans signaling). Appraisal of IL-6R expression on human and mouse T cells emphasized that IL-6R expression is closely linked with that of CCR7 and CD62L. In this regard, infiltrating effector T cells from clinical and experimental peritonitis episodes lose IL-6R expression, and anti-CD3/CD28 Ab costimulation of peripheral T cells in vitro leads to a downregulation in IL-6R expression. Consequently, IL-6 signaling through membrane-bound IL-6R seems to be limited to naive or central memory T cell populations. Loss of IL-6R expression by activated T cells further suggests that these effector cells might still retain IL-6 responsiveness via IL-6 trans signaling. Using IL-6R–deficient mice and recombinant tools that modulate the capacity of IL-6 to signal via its soluble receptor, we report that local control of IL-6 trans signaling regulates the effector characteristics of the T cell infiltrate and promotes the maintenance of IL-17A–secreting CD4+ T cells. Therefore, we concluded that classical IL-6R signaling in naive or central memory CD4+ T cells is required to steer their effector characteristics, whereas local regulation of soluble IL-6R activity might serve to maintain the cytokine profile of the Th cell infiltrate. Therefore, the activation status of a T cell population is linked with an alteration in IL-6 responsiveness.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RZ Other systems of medicine
Publisher: American Association of Immunologists
ISSN: 0022-1767
Last Modified: 08 Aug 2018 00:41
URI: http://orca.cf.ac.uk/id/eprint/24878

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