title: Atorvastatin-modified dendritic cells in vitro ameliorate experimental autoimmune myasthenia gravis by up-regulated Treg cells and shifted Th1/Th17 to Th2 cytokines.
abstract: Conventional therapies for autoimmune diseases produce nonspecific immune suppression, which are usually continued lifelong to maintain disease control, and associated with a variety of adverse effects. In this study, we found that spleen-derived dendritic cells (DCs) from the ongoing experimental autoimmune myasthenia gravis (EAMG) rats can be induced into tolerogenic DCs by atorvastatin in vitro. Administration of these tolerogenic DCs to EAMG rats on days 5 and 13 post immunization (p.i.) resulted in improved clinical symptoms, which were associated with increased numbers of CD4(+)CD25(+) T regulatory (Treg) cells and Foxp3 expression, decreased lymphocyte proliferation among lymph node mononuclear cells (MNC), shifted cytokine profile from Th1/Th17 to Th2 type cytokines, decreased level of anti-R97-116 peptide (region 97-116 of the rat acetylcholine receptor α subunit) IgG antibody in serum. These tolerogenic DCs can migrate to spleen, thymus, popliteal and inguinal lymph nodes after they were injected into the EAMG rats intraperitoneally. Furthermore, these tolerogenic DCs played their immunomodulatory effects in vivo mainly by decreased expression of CD86 and MHC class II on endogenous DCs. All these data provided us a new strategy to treat EAMG and even human myasthenia gravis (MG).
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Cao
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.forename: Long-Tao
authors.initials: LT
authors.lastname: Yue
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Xiu-Hua
authors.initials: XH
authors.lastname: Li
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Dou
authors.forename: Rui-Sheng
authors.initials: RS
authors.lastname: Duan
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D007167:Immunotherapy; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin
keywords: Atorvastatin; Cytokines; Dendritic cells; Experimental autoimmune myasthenia gravis; Treg cells