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Immunity. 2011 Mar 25;34(3):409-21. doi: 10.1016/j.immuni.2011.02.011.

Foxp3(+) regulatory T cells promote T helper 17 cell development in vivo through regulation of interleukin-2.

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Merck Research Laboratories, 901 California Avenue, Palo Alto, CA 94304, USA.


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.

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  • Immunotherapy. 2011 Jul;3(7):821-3.
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