title: A20 plays a critical role in the immunoregulatory function of mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) possess an immunoregulatory capacity and are a therapeutic target for many inflammation-related diseases. However, the detailed mechanisms of MSC-mediated immunosuppression remain unclear. In this study, we provide new information to partly explain the molecular mechanisms of immunoregulation by MSCs. Specifically, we found that A20 expression was induced in MSCs by inflammatory cytokines. Knockdown of A20 in MSCs resulted in increased proliferation and reduced adipogenesis, and partly reversed the suppressive effect of MSCs on T cell proliferation in vitro and inhibited tumour growth in vivo. Mechanistic studies indicated that knockdown of A20 in MSCs inhibited activation of the p38 mitogen-activated protein kinase (MAPK) pathway, which potently promoted the production of tumour necrosis factor (TNF)-α and inhibited the production of interleukin (IL)-10. Collectively, these data reveal a crucial role of A20 in regulating the immunomodulatory activities of MSCs by controlling the expression of TNF-α and IL-10 in an inflammatory environment. These findings provide novel insights into the pathogenesis of various inflammatory-associated diseases, and are a new reference for the future development of treatments for such afflictions.
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Haidian District, Beijing, China.|Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Haidian District, Beijing, China.
authors.forename: Rui-Jie
authors.initials: RJ
authors.lastname: Dang
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Haidian District, Beijing, China.|Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Haidian District, Beijing, China.
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Yang
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Haidian District, Beijing, China.|Department of Biology and Chemical Engineering, Tongren University, Tongren City, Guizhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Beijing Aiyuhua Hospital for Children and Women, Beijing, China.
authors.forename: Dian-Chao
authors.initials: DC
authors.lastname: Cui
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Bangxing
authors.initials: B
authors.lastname: Hong
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Haidian District, Beijing, China.|Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Haidian District, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Haidian District, Beijing, China.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Haidian District, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Haidian District, Beijing, China.
authors.forename: Qi-Yu
authors.initials: QY
authors.lastname: Wang
authors.affiliation: Department of Experimental Hematology, Institute of Radiation Medicine, Beijing, China.
authors.forename: Fengjun
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Haidian District, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Mao
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Haidian District, Beijing, China.
authors.forename: Changyong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Haidian District, Beijing, China.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Jiang
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Haidian District, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wen
mesh_terms: D050156:Adipogenesis; D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D055785:Gene Knockdown Techniques; D007165:Immunosuppression Therapy; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D034741:RNA, Small Interfering; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; C513261:Tnfaip3 protein, mouse; D015232:Dinoprostone
keywords: A20; immunoregulation; mesenchymal stem cells