title: Statin-modified dendritic cells regulate humoral immunity in experimental autoimmune myasthenia gravis.
abstract: We previously demonstrated that atorvastatin induced immature dendritic cells (DCs) derived from spleen in vitro. Administration of these tolerogenic DCs led to amelioration of experimental autoimmune myasthenia gravis (EAMG). The protective effect was mainly mediated by inhibited cellular immune response, including up-regulated regulatory T cells and shifted Th1/Th17 to Th2 cytokines. The present study employed atorvastatin-modified bone marrow-derived DCs (AT-BMDCs) to explore the effect of tolerogenic DCs on humoral immune response of EAMG and further elucidate the underlying mechanisms. Our data showed that AT-BMDCs reduced the quantity and the relative affinity of pathogenic antibodies, suppressed germinal center response, decreased follicular helper T cells and IL-21, and increased regulatory B cells. These results suggest that AT-BMDCs ameliorate EAMG by regulating humoral immune response, thus providing new insights into therapeutic approaches of myasthenia gravis and other autoimmune diseases.
authors: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors: Heng
authors: H
authors: Li
authors: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors: Cong-Cong
authors: CC
authors: Wang
authors: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors: Min
authors: M
authors: Zhang
authors: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors: Xiao-Li
authors: XL
authors: Li
authors: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors: Peng
authors: P
authors: Zhang
authors: Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors: Long-Tao
authors: LT
authors: Yue
authors: Department of Neurology, Jinan General Military Hospital, Second Military Medical University, Jinan 250031, PR China.
authors: Shuai
authors: S
authors: Miao
authors: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors: Shan
authors: S
authors: Wang
authors: Department of Electromyography, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors: Ying
authors: Y
authors: Liu
authors: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors: Yan-Bin
authors: YB
authors: Li
authors: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China. Electronic address: ruisheng_duan@yahoo.com.
authors: Rui-Sheng
authors: RS
authors: Duan
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D056724:Immunity, Humoral / Q000187:drug effects*; D007378:Interleukins / Q000378:metabolism; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology; D013997:Time Factors; D000098546:Interleukin-21
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D000949:Histocompatibility Antigens Class II; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007378:Interleukins; D011950:Receptors, Cholinergic; D000069059:Atorvastatin; D000098546:Interleukin-21
keywords: Dendritic cells; Experimental autoimmune myasthenia gravis; Follicular helper T cells; Humoral immunity; Regulatory B cells; Statin