title: Transcription factor IRF8 controls Th1-like regulatory T-cell function.
abstract: Recent studies have suggested that regulatory T (Treg) cells comprise a heterogeneous population that regulates various aspects of the immune response, and that Treg cells use the factors that are expressed in their target cells to regulate them. We searched for factors that regulate Th1 response in Treg cells using a meta-analysis. In the process, we discovered that transcription factor interferon regulatory factor 8 (IRF8) was selectively expressed in Treg and Th1 cells. IRF8-deficient Treg cells showed defective expression of CXCR3 and aberrant expression of the Il4 and Il17 genes. Upon treatment with alpha galactosyl-C18-ceramide (αGal-C18-Cer), IRF8-deficient mice showed defective Treg cell recruitment in the liver. Eliciting Th1 immune response by anti-CD40 antibody injection in mice induced IRF8 expression in Treg cells. The expression of IRF8 was induced by Foxp3 in Treg cells. IRF8 had no effect on T-bet expression in Treg and vice versa. Thus, our results strongly suggest that IRF8 controls Th1 immune response in Treg cells independent of T-bet.
authors.affiliation: Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul, 121-742, Korea
authors.forename: Wonyong
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul, 121-742, Korea
authors.forename: Hyeong Su
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul, 121-742, Korea
authors.forename: Song Yi
authors.initials: SY
authors.lastname: Baek
authors.affiliation: Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul, 121-742, Korea
authors.forename: Gap Ryol
authors.initials: GR
authors.lastname: Lee
mesh_terms: D000818:Animals; D002518:Ceramides; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006505:Hepatitis / Q000276:immunology / Q000473:pathology; D007111:Immunity, Cellular; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D050835:Interferon Regulatory Factors / Q000172:deficiency / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D054367:Receptors, CXCR3 / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D015854:Up-Regulation; D000098815:T-bet Transcription Factor; D000099185:Interferon Regulatory Factor-8
chemical_list: D002518:Ceramides; D051858:Forkhead Transcription Factors; D050835:Interferon Regulatory Factors; D020381:Interleukin-17; D015847:Interleukin-4; D054367:Receptors, CXCR3; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D000099185:Interferon Regulatory Factor-8; C515188:Cxcr3 protein, mouse; C498833:Foxp3 protein, mouse