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The PPARα pathway in Vγ9Vδ2 T cell anergy

Abstract : Phosphoantigens (PAgs) activate Vγ9Vδ2 T lymphocytes, inducing their potent and rapid response in vitro and in vivo. However, humans and nonhuman primates that receive repeated injections of PAgs progressively lose their Vγ9Vδ2 T cell response to them. To elucidate the molecular mechanisms of this in vivo desensitization, we analyzed the transcriptome of circulating Vγ9Vδ2 T cells from macaques injected with PAg. We showed that three PAg injections induced the activation of the PPARα pathway in Vγ9Vδ2 T cells. Thus, we analyzed the in vitro response of Vγ9Vδ2 T cells stimulated with a PPARα agonist. We demonstrated that in vitro PPARα pathway activation led to the inhibition of the BrHPP-induced activation and proliferation of human Vγ9Vδ2 T cells. Since the PPARα pathway is involved in the antigen-selective desensitization of human Vγ9Vδ2 T cells, the use of PPARα inhibitors could enhance cancer immunotherapy based on Vγ9Vδ2 T cells.
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Contributor : Mary Poupot Connect in order to contact the contributor
Submitted on : Monday, February 10, 2020 - 9:52:32 AM
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Mary Poupot, Frédéric Boissard, Delphine Bétous, Laure Bardouillet, Séverine Fruchon, et al.. The PPARα pathway in Vγ9Vδ2 T cell anergy. Cellular and Molecular Biology Letters, Springer Verlag (Germany), 2014, 19 (4), pp.649-58. ⟨10.2478/s11658-014-0218-0⟩. ⟨inserm-02472220⟩



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