Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells

E Bettelli, Y Carrier, W Gao, T Korn, TB Strom, M Oukka… - Nature, 2006 - nature.com
E Bettelli, Y Carrier, W Gao, T Korn, TB Strom, M Oukka, HL Weiner, VK Kuchroo
Nature, 2006nature.com
On activation, T cells undergo distinct developmental pathways, attaining specialized
properties and effector functions. T-helper (TH) cells are traditionally thought to differentiate
into TH1 and TH2 cell subsets. TH1 cells are necessary to clear intracellular pathogens and
TH2 cells are important for clearing extracellular organisms,. Recently, a subset of
interleukin (IL)-17-producing T (TH17) cells distinct from TH1 or TH2 cells has been
described and shown to have a crucial role in the induction of autoimmune tissue injury,,. In …
Abstract
On activation, T cells undergo distinct developmental pathways, attaining specialized properties and effector functions. T-helper (TH) cells are traditionally thought to differentiate into TH1 and TH2 cell subsets. TH1 cells are necessary to clear intracellular pathogens and TH2 cells are important for clearing extracellular organisms,. Recently, a subset of interleukin (IL)-17-producing T (TH17) cells distinct from TH1 or TH2 cells has been described and shown to have a crucial role in the induction of autoimmune tissue injury,,. In contrast, CD4+CD25+Foxp3+ regulatory T (Treg) cells inhibit autoimmunity and protect against tissue injury. Transforming growth factor-β (TGF-β) is a critical differentiation factor for the generation of Treg cells. Here we show, using mice with a reporter introduced into the endogenous Foxp3 locus, that IL-6, an acute phase protein induced during inflammation,, completely inhibits the generation of Foxp3+ Treg cells induced by TGF-β. We also demonstrate that IL-23 is not the differentiation factor for the generation of TH17 cells. Instead, IL-6 and TGF-β together induce the differentiation of pathogenic TH17 cells from naive T cells. Our data demonstrate a dichotomy in the generation of pathogenic (TH17) T cells that induce autoimmunity and regulatory (Foxp3+) T cells that inhibit autoimmune tissue injury.
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