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Foxd3 suppresses interleukin‐10 expression in B cells
Author(s) -
Zhang Yu,
Wang Zhiding,
Xiao He,
Liu Xiaoling,
Zhu Gaizhi,
Yu Dandan,
Han Gencheng,
Chen Guojiang,
Hou Chunmei,
Ma Ning,
Shen Beifen,
Li Yan,
Wang Tianxiao,
Wang Renxi
Publication year - 2017
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.12701
Subject(s) - chromatin immunoprecipitation , transcription factor , biology , interleukin 10 , promoter , regulatory b cells , cytokine , microbiology and biotechnology , immunology , gene expression , gene , genetics
Summary Interleukin‐10‐positive (IL‐10 + ) regulatory B (Breg) cells play an important role in restraining excessive inflammatory responses by secreting IL‐10. However, it is still unclear what key transcription factors determine Breg cell differentiation. Hence, we explore what transcription factor plays a key role in the expression of IL‐10, a pivotal cytokine in Breg cells. We used two types of web‐based prediction software to predict transcription factors binding the IL‐10 promoter and found that IL‐10 promoter had many binding sites for Foxd3. Chromatin immunoprecipitation PCR assay demonstrated that Foxd3 directly binds the predicted binding sites around the start codon upstream by −1400 bp. Further, we found that Foxd3 suppressed the activation of IL‐10 promoter by using an IL‐10 promoter report system. Finally, knocking out Foxd3 effectively promotes Breg cell production by up‐regulating IL‐10 expression. Conversely, up‐regulated Foxd3 expression was negatively associated with IL‐10 + Breg cells in lupus‐prone MRL/lpr mice. Hence, our data suggest that Foxd3 suppresses the production of IL‐10 + Breg cells by directly binding the IL‐10 promoter. This study demonstrates the mechanism for Breg cell production and its application to the treatment of autoimmune diseases by regulating Foxd3 expression.