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.CAN-12-4018

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Title		SOCS3 transactivation by PPARγ prevents IL-17-driven cancer growth
Authors		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 show all authors [1 - 18]
Published in		Cancer Research. 2013, vol. 73, no. 12, p. 3578-90
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.
Keywords		Animals — Blotting, Western — CD4-Positive T-Lymphocytes/drug effects/metabolism — Cell Differentiation/drug effects — Cell Line, Tumor — Diet — Docosahexaenoic Acids/administration & dosage/pharmacology — Female — Interleukin-17/metabolism — Mammary Neoplasms, Experimental/genetics/pathology/prevention & control — Mice — Mice, Inbred BALB C — Mice, Inbred C57BL — Mice, Knockout — Mice, Nude — PPAR gamma/agonists/genetics/metabolism — Promoter Regions, Genetic/genetics — RNA Interference — Reverse Transcriptase Polymerase Chain Reaction — Suppressor of Cytokine Signaling Proteins/genetics/metabolism — Th17 Cells/drug effects/metabolism — Transcriptional Activation — Tumor Burden/drug effects/genetics
Identifiers		DOI: 10.1158/0008-5472.CAN-12-4018 PMID: 23619236
Full text		Article (Published version) (859 Kb) - Free access
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group		Groupe Pot-Kreis Caroline (931)
Citation (ISO format)		BERGER, Hélène et al. SOCS3 transactivation by PPARγ prevents IL-17-driven cancer growth. In: Cancer research, 2013, vol. 73, n° 12, p. 3578-90. doi: 10.1158/0008-5472.CAN-12-4018 https://archive-ouverte.unige.ch/unige:33010