title: Foxp3(+) regulatory T cells promote T helper 17 cell development in vivo through regulation of interleukin-2.
abstract: T helper 17 (Th17) cell development is driven by cytokines including transforming growth factor-β (TGF-β), interleukin-6 (IL-6), IL-1, and IL-23. Regulatory T (Treg) cells can provide the TGF-β in vitro, but their role in vivo remains unclear, particularly because Treg cells inhibit inflammation in many models of Th17 cell-associated autoimmunity. We used mice expressing Diphtheria toxin receptor under control of the Foxp3 promoter to deplete Foxp3(+) Treg cells in adult mice during in vivo Th17 cell priming. Treg cell depletion resulted in a reduced frequency of antigen-specific IL-17 producers in draining lymph nodes and blood, correlating with reduced inflammatory skin responses. In contrast, Treg cells did not promote IL-17 secretion after initial activation stages. Treg cell production of TGF-β was not required for Th17 cell promotion, and neither was suppression of Th1 cell-associated cytokines. Rather, regulation of IL-2 availability and resultant signaling through CD25 by Treg cells was found to play an important role.
authors: Merck Research Laboratories, 901 California Avenue, Palo Alto, CA 94304, USA.
authors: Yi
authors: Y
authors: Chen
authors: Christopher J
authors: CJ
authors: Haines
authors: Ilona
authors: I
authors: Gutcher
authors: Kristin
authors: K
authors: Hochweller
authors: Wendy M
authors: WM
authors: Blumenschein
authors: Terrill
authors: T
authors: McClanahan
authors: Günter
authors: G
authors: Hämmerling
authors: Ming O
authors: MO
authors: Li
authors: Daniel J
authors: DJ
authors: Cua
authors: Mandy J
authors: MJ
authors: McGeachy
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D007376:Interleukin-2