TLR9 mediated regulatory B10 cell amplification following sub-total body irradiation: Implications in attenuating EAE. (March 2017)

• Record Type: Journal Article
• Authors: Hong, Jinsheng; Fang, Jie; Lan, Ruilong; Tan, Qi; Tian, Yeping; Zhang, Mei; Okunieff, Paul; Zhang, Lurong; Lin, Jianhua; Han, Deping
• Is Part Of: Molecular immunology. Volume 83(2017:Mar.)
• Page Start: 52
• Page End: 61
• Publication Date: 2017-03
• Subjects: Breg regulatory B cell -- B10 cell IL-10-producing B cell -- EAE experimental autoimmune encephalomyelitis -- MOG myelin oligodendrocyte glycoprotein -- MS multiple sclerosis -- MyD88 myeloid differentiation primary response gene 88 -- Sub-TBI sub-total body irradiation -- TRIF Toll-IL-1R domain-containing adapter-inducing IFN-β -- WT wild-type; Breg/B10 cells -- TLR9 -- IL-10 -- MyD88 -- Autoimmunity; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2017.01.011
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: Spleen Breg/B10 cell frequencies were expanded three weeks after Sub-TBI in wild type mice but not in TLR9-/- mice. Sub-TBI induced Breg/B10 cells dramatically inhibit disease onset and severity when transferred into mice with established EAE. Adoptively transferred Sub-TBI induced Breg cells significantly suppress responses of TH17 and TH1 in EAE mice. Abstract: Autoimmunity and inflammation are controlled in part by regulatory B (Breg) cells, including the recently identified IL-10-competent B10 cell subset that represents 1%–3% of mouse spleen B cells. In this study, the influence of irradiation on Breg/B10 cell generation and IL-10 production mediated by TLR9 signaling pathways was investigated. Spleen and peritoneal cavity Breg/B10 cell frequencies were significantly expanded three weeks after sub-total body irradiation (sub-TBI, 5 Gy or 10 Gy) in adult male wild type (WT) C57BL/6(B6) mice but not in TLR9 −/− mice. TLR9 agonist ODN1826 stimulation in vitro for 5 h induced more B10 cells to express cytoplasmic IL-10 in sub-TBI WT mice than in TLR9 −/− mice. Prolonged ODN1826 stimulation (48 h) induced additional spleen CD19 hi CD5 + CD1d hi B cells to express IL-10. TLR9-dependent signaling molecules, MyD88, TRAF6 and IRF8 are involved in sub-TBI induced Breg/B10 cells development and expansion. Furthermore, using a mouse model for multiple sclerosis, we show here that sub-TBI induced Breg/B10 cells dramatically inhibit disease onset and severity when transferred into mice with established experimental autoimmune encephalomyelitis (EAE). Adoptively transferred sub-TBI induced Breg cells significantly suppress inflammatory T cell responses of TH17 and TH1 types in EAE mice. In conclusion, sub-TBI can drive Breg/B10 cell development and expansion, which could be used as a novel tool for suppressing undesirable immunity. The ex vivo expansion and reinfusion of autologous Breg/B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.