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J Immunol. 2010 Feb 15;184(4):2130-9. doi: 10.4049/jimmunol.0901528. Epub 2010 Jan 18.

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.

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  • 1Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, Wales, UK.

Abstract

IL-6 responses are classically orchestrated via a membrane-bound IL-6R (CD126) alpha 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.

PMID:
20083667
[PubMed - indexed for MEDLINE]
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