Fiche publication
Date publication
décembre 2017
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BOIDOT Romain
,
Pr GHIRINGHELLI François
,
Dr LADOIRE Sylvain
,
Dr VEGRAN Frédérique
,
Dr CHALMIN Fanny
,
Dr LIMAGNE Emeric
,
Dr DERANGERE Valentin
,
Dr THIBAUDIN Marion
Tous les auteurs :
Humblin E, Thibaudin M, Chalmin F, Derangère V, Limagne E, Richard C, Flavell RA, Chevrier S, Ladoire S, Berger H, Boidot R, Apetoh L, Végran F, Ghiringhelli F
Lien Pubmed
Résumé
Interferon regulatory factors (IRF) have critical functions in lymphoid development and in immune response regulation. Although many studies have described the function of IRF4 in CD4 T cells, few have focused on the IRF4 homologue, IRF8. Here, we show that IRF8 is required for Th9 differentiation in vitro and in vivo. IRF8 functions through a transcription factor complex consisting of IRF8, IRF4, PU.1 and BATF, which binds to DNA and boosts Il9 transcription. By contrast, IRF8 deficiency promotes the expression of other genes such as Il4, as IRF8 dimerises with the transcriptional repressor ETV6 and inhibits Il4 expression. In vivo, IRF8 is essential for the anti-tumour effects of Th9 cells in mouse melanoma models. Our results show that IRF8 complexes boost the Th9 program and repress Il4 expression to modulate Th9 cell differentiation, thereby implicating IRF8 as a potential therapeutic target to affect Th9 responses in cancer therapy.
Mots clés
Animals, Basic-Leucine Zipper Transcription Factors, metabolism, Cell Differentiation, genetics, Female, Gene Knockdown Techniques, Humans, Interferon Regulatory Factors, genetics, Interleukin-9, metabolism, Melanoma, immunology, Mice, Mice, Inbred C57BL, Proto-Oncogene Proteins, metabolism, RNA, Small Interfering, metabolism, T-Lymphocytes, Helper-Inducer, immunology, Trans-Activators, metabolism, Transcription, Genetic, immunology, Xenograft Model Antitumor Assays
Référence
Nat Commun. 2017 Dec 12;8(1):2085
