title: IFN-β induces the proliferation of CD4+CD25+Foxp3+ regulatory T cells through upregulation of GITRL on dendritic cells in the treatment of multiple sclerosis.
abstract: IFN-β is a major disease-modifying agent used for the treatment of multiple sclerosis (MS). Its mechanisms are complex and it has broad immunomodulatory effects on many types of immune cells. It was observed clinically that the quantity of CD4(+)CD25(+)Foxp3(+) regulatory T cells increases in some MS patients treated with IFN-β. In this study, we show that IFNAR engagement by IFN-β expands naturally occurring CD4(+)CD25(+)Foxp3(+) regulatory T cell population through the modulation of dendritic cells (DCs). IFN-β has no effect on the conversion of CD4(+)CD25(-) T cells to adaptive Treg cells. The IFN-β-induced upregulation of GITRL on DC and downregulation of CTLA-4 on Treg cell work together to facilitate the proliferation of anergic Treg cells. In MS patients treated with Avonex or Rebif (IFN-β), it was found that GITRL expression is markedly upregulated on peripheral CD14(+) cells. Our findings help the better understanding of the complex effects of IFN-β in the treatment of MS.
authors: Multiple Sclerosis Research Unit, Department of Neurology and Baylor Multiple Sclerosis Center, Baylor College of Medicine, Houston, USA.
authors: Meiyue
authors: M
authors: Chen
authors: Guangjie
authors: G
authors: Chen
authors: Shaohua
authors: S
authors: Deng
authors: Xin
authors: X
authors: Liu
authors: George J
authors: GJ
authors: Hutton
authors: Jian
authors: J
authors: Hong
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000096:biosynthesis*; D006801:Humans; D016899:Interferon-beta / Q000502:physiology* / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D053450:Glucocorticoid-Induced TNFR-Related Protein; D016899:Interferon-beta