title: Foxp3⁺ Treg cells in the inflamed CNS are insensitive to IL-6-driven IL-17 production.
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.
authors.affiliation: Centre for Multiple Sclerosis Research and Centre for Immunology Infection and Evolution, Queen's Medical Research Institute, Medical Research Council/University of Edinburgh Centre for Inflammation Research, Edinburgh, UK.
authors.forename: Richard A
authors.initials: RA
authors.lastname: O'Connor
authors.forename: Stefan
authors.initials: S
authors.lastname: Floess
authors.forename: Jochen
authors.initials: J
authors.lastname: Huehn
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Anderton
mesh_terms: D000818:Animals; D050822:Cytokine Receptor gp130 / Q000096:biosynthesis / Q000276:immunology; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology*; D020381:Interleukin-17 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000276:immunology*; D051379:Mice; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C113250:interleukin-6 receptor alpha; D050822:Cytokine Receptor gp130