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Forkhead transcription factor FOXO 3a mediates interferon‐ γ ‐induced MHC II transcription in macrophages
Author(s) -
Wu Xiaoyan,
Fan Zhiwen,
Chen Ming,
Chen Yi,
Rong Danyan,
Cui Zhiwei,
Yuan Yibiao,
Zhuo Lili,
Xu Yong
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13116
Subject(s) - ciita , transcription factor , mhc class ii , major histocompatibility complex , biology , transcription (linguistics) , microbiology and biotechnology , promoter , stat protein , gene expression , antigen , signal transduction , gene , immunology , genetics , stat3 , linguistics , philosophy
Summary Macrophages are professional antigen‐presenting cells relying on the expression of class II major histocompatibility complex ( MHC II ) genes. Interferon‐ γ ( IFN ‐ γ ) activates MHC II transcription via the assembly of an enhanceosome centred on class II trans‐activator ( CIITA ). In the present study, we investigated the role of the forkhead transcription factor FOXO 3a in IFN ‐ γ ‐induced MHC II transcription in macrophages. Knockdown of FOXO 3a, but not FOXO 1 or FOXO 4, diminished IFN ‐ γ ‐induced MHC II expression in RAW cells. On the contrary, over‐expression of FOXO 3a, but neither FOXO 1 nor FOXO 4, enhanced CIITA ‐mediated trans‐activation of the MHC II promoter. IFN ‐ γ treatment promoted the recruitment of FOXO 3a to the MHC II promoter. Co‐immunoprecipitation and RE ‐Ch IP assays showed that FOXO 3a was a component of the MHC II enhanceosome forming interactions with CIITA , RFX 5, RFXB and RFXAP . FOXO 3a contributed to MHC II transcription by altering histone modifications surrounding the MHC II promoter. Of interest, FOXO 3a was recruited to the type IV CIITA promoter and directly activated CIITA transcription by interacting with signal transducer of activation and transcription 1 in response to IFN ‐ γ stimulation. In conclusion, our data unveil a novel role for FOXO 3a in the regulation of MHC II transcription in macrophages.