Supplementary Figure 5 from SOCS3 Transactivation by PPARγ Prevents IL-17–Driven Cancer Growth

Berger, Hélène; Végran, Frédérique; Chikh, Madijd; Gilardi, Federica; Ladoire, Sylvain; Bugaut, Hélène; Mignot, Grégoire; Chalmin, Fanny; Bruchard, Mélanie; Derangère, Valentin; Chevriaux, Angélique; Rébé, Cédric; Ryffel, Bernhard; Pot, Caroline; Hichami, Aziz; Desvergne, Béatrice; Ghiringhelli, François; Apetoh, Lionel

doi:10.1158/0008-5472.22394477.v1

Supplementary Figure 5 from SOCS3 Transactivation by PPARγ Prevents IL-17–Driven Cancer Growth

journal contribution

posted on 2023-03-30, 21:25 authored by Hélène Berger, Frédérique Végran, Madijd Chikh, Federica Gilardi, Sylvain Ladoire, Hélène Bugaut, Grégoire Mignot, Fanny Chalmin, Mélanie Bruchard, Valentin Derangère, Angélique Chevriaux, Cédric Rébé, Bernhard Ryffel, Caroline Pot, Aziz Hichami, Béatrice Desvergne, François Ghiringhelli, Lionel Apetoh

PDF file - 46K, Blockade of IL-17 by monoclonal antibody does not exert any cytotoxic effect on mammary tumor cells in vitro.

History

ARTICLE ABSTRACT

Activation of the transcription factor PPARγ by the n-3 fatty acid docosahexaenoic acid (DHA) is implicated in controlling proinflammatory cytokine secretion, but the intracellular signaling pathways engaged by PPARγ are incompletely characterized. Here, we identify the adapter-encoding gene SOCS3 as a critical transcriptional target of PPARγ. SOCS3 promoter binding and gene transactivation by PPARγ was associated with a repression in differentiation of proinflammatory T-helper (TH)17 cells. Accordingly, TH17 cells induced in vitro displayed increased SOCS3 expression and diminished capacity to produce interleukin (IL)-17 following activation of PPARγ by DHA. Furthermore, naïve CD4 T cells derived from mice fed a DHA-enriched diet displayed less capability to differentiate into TH17 cells. In two different mouse models of cancer, DHA prevented tumor outgrowth and angiogenesis in an IL-17–dependent manner. Altogether, our results uncover a novel molecular pathway by which PPARγ-induced SOCS3 expression prevents IL-17–mediated cancer growth. Cancer Res; 73(12); 3578–90. ©2013 AACR.