title: Dimethyl sulfoxide inhibits spontaneous diabetes and autoimmune recurrence in non-obese diabetic mice by inducing differentiation of regulatory T cells.
abstract: Type 1 diabetes mellitus (T1D) is caused by the destruction of insulin-producing β cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective therapeutic strategy for T1D. However, the survival of islet grafts can be disrupted by recurrent autoimmunity. Dimethyl sulfoxide (DMSO) is a solvent for organic and inorganic substances and an organ-conserving agent used in solid organ transplantations. DMSO also exerts anti-inflammatory, reactive oxygen species scavenger and immunomodulatory effects and therefore exhibits therapeutic potential for the treatment of several human inflammatory diseases. In this study, we investigated the therapeutic potential of DMSO in the inhibition of autoimmunity. We treated an animal model of islet transplantation (NOD mice) with DMSO. The survival of the syngeneic islet grafts was significantly prolonged. The population numbers of CD8, DC and Th1 cells were decreased, and regulatory T (Treg) cell numbers were increased in recipients. The expression levels of IFN-γ and proliferation of T cells were also reduced following DMSO treatment. Furthermore, the differentiation of Treg cells from naive CD4 T cells was significantly increased in the in vitro study. Our results demonstrate for the first time that in vivo DMSO treatment suppresses spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Treg cells.
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Gu-Jiun
authors.initials: GJ
authors.lastname: Lin
authors.affiliation: Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
authors.affiliation: Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Jyh-Cherng
authors.initials: JC
authors.lastname: Yu
authors.affiliation: School of Dentistry, National Defense Medical Center, Taipei, Taiwan, ROC; Department of Oral and Maxillofacial Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Yuan-Wu
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC; School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Kuo
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC; Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Chiao-Chi
authors.initials: CC
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Hao-Ming
authors.initials: HM
authors.lastname: Chang
authors.affiliation: Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: De-Chuan
authors.initials: DC
authors.lastname: Chan
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC; Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC. Electronic address: h610129@gmail.com.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Huang
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003920:Diabetes Mellitus / Q000517:prevention & control*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D004121:Dimethyl Sulfoxide
keywords: Autoimmune recurrence; Dimethyl sulfoxide; Islet transplantation; NOD mice; Regulatory T cell; Type 1 diabetes