Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation.
By A. Laurence, C. Tato, Todd S. Davidson, Y. Kanno, Zhi Chen, Zhengju Yao, R. Blank, F. Meylan, R. Siegel, L. Hennighausen and 2 more. Immunity, 2007
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Recent work has identified a new subset of effector T cells that produces interleukin (IL)-17 known as T helper 17 (Th17) cells, which is involved in the pathophysiology of inflammatory diseases and is thought to be developmentally related to regulatory T (Treg) cells. Because of its importance for Treg cells, we examined the role of IL-2 in Th17 generation and demonstrate that a previously unrecognized aspect of IL-2 function is to constrain IL-17 production. Genetic deletion or antibody blockade of IL-2 promoted differentiation of the Th17 cell subset. Whereas STAT3 appeared to be a key positive regulator of RORgammat and IL-17 expression, absence of IL-2 or disruption of its signaling by deletion of the transcription factor STAT5 resulted in enhanced Th17 cell development. We conclude that in addition to the promotion of activation-induced cell death of lymphocytes and the generation of Treg cells, inhibition of Th17 polarization appears to be an important function of IL-2.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/219ae76d99a0746249db47daa8dc94fab72b0f98
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Citations in the corpus
- Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17–producing human T helper cells (2007, background): “Several cytokines, including type I and type II interferon, IL-4, IL-12, IL-27 and IL-2, inhibit T H -17 differentiatio”
- The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells (2017, background): “RORc is more likely to be inhibited by STAT5 than induced by this factor, therefore, STAT5A and STAT5B are important negative regulators of Th17 differentiation [46].”
- Interleukin-2 at the Crossroads of Effector Responses, Tolerance, and Immunotherapy (2013, neutral): “, 2008), while inhibiting Th17 (Laurence et al., 2007) and T follicular helper (Tfh) cell (Ballesteros-Tato et al.”
- Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism (2009, background): “Cells deficient in IL-6 do neither express RORγt nor IL-17F and IL23R [Korn et al., 2007a; Laurence et al., 2007;Yang et al., 2007b].”
- Critical regulation of early Th17 cell differentiation by IL-1 signaling (2009, background): “We found that Th17 cells expressed higher amounts of IL-1R1 mRNA, which was dependent on STAT3, RORa, and RORgt.”
- Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell Pathogenicity and Homeostasis (2010, background): “Accordingly, we and others have shown that STAT3 plays a critical role in the differentiation of CD4+ T cells into Th17 cells (Chen et al., 2006; Laurence et al., 2007; Mathur et al., 2007; Wei et al., 2007; Yang et al., 2007).”
- Generation of follicular helper T cells is mediated by IL-21 but independent of TH1, TH2 or TH17 lineages (2008, methodology): “Stat3f/f mice (Takeda et al., 1999) were bred with CD4-Cre mice provided by C. Wilson (Lee et al., 2001).”