title: Foxd3 suppresses interleukin-10 expression in B cells.
abstract: 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.
authors.affiliation: College of Pharmacy, Henan University, Kaifeng, China.|Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.|Department of Biomedicine, Institute of Frontier Medical Sciences, School of Pharmaceutical Sciences, Jilin University, Changchun, China.
authors.forename: Zhiding
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.|Department of Nephrology, The 307th Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.|Laboratory of Cellular and Molecular Immunology, Henan University, Kaifeng, Henan, China.
authors.forename: Gaizhi
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Yu
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Guojiang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Hou
authors.affiliation: Department of Rheumatology, First Hospital of Jilin University, Changchun, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Pharmacy, Henan University, Kaifeng, China.
authors.forename: Tianxiao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Renxi
authors.identifier: 0000-0003-4130-3334
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D019295:Computational Biology; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; C101757:Foxd3 protein, mouse; C556062:IL10 protein, mouse; D012097:Repressor Proteins; D016753:Interleukin-10
keywords: Foxd3; interleukin-10; lupus-prone mice; regulatory B cells