Foxp3+Treg cells in the inflamed CNS are insensitive to IL-6-driven IL-17 production

O'Connor, Richard A., Floess, Stefan, Huehn, Jochen, Jones, Simon Arnett ORCID: https://orcid.org/0000-0001-7297-9711 and Anderton, Stephen M. 2012. Foxp3+Treg cells in the inflamed CNS are insensitive to IL-6-driven IL-17 production. European Journal of Immunology 42 (5) , pp. 1174-1179. 10.1002/eji.201142216

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Abstract

Foxp3+ T regulatory (Treg) cells can be induced to produce interleukin (IL)-17 by in vitro exposure to proinflammatory cytokines, drawing into question their functional stability at sites of inflammation. Unlike their splenic counterparts, Treg cells from the inflamed central nervous system (CNS-Treg cells) during EAE resisted conversion to IL-17 production when exposed to IL-6. We show that the highly activated phenotype of CNS-Treg cells includes elevated expression of the Th1-associated molecules CXCR3 and T-bet, but reduced expression of the IL-6 receptor α chain (CD126) and the signaling chain gp130. We found a lack of IL-6 receptor on all CNS CD4+ T cells, which was reflected by an absence of both classical and trans-IL-6 signaling in CNS CD4+ cells, compared with their splenic counterparts. We propose that extinguished responsiveness to IL-6 (via down-regulation of CD126 and gp130) stabilizes the regulatory phenotype of activated Treg cells at sites of autoimmune inflammation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > R Medicine (General)
Uncontrolled Keywords:	EAE; Foxp3; IL-6; IL-17; Treg cells
Publisher:	John Wiley & Sons
ISSN:	0014-2980
Last Modified:	21 Oct 2022 10:49
URI:	https://orca.cardiff.ac.uk/id/eprint/41456

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