title: Caspase-1 inhibitor ameliorates experimental autoimmune myasthenia gravis by innate dendric cell IL-1-IL-17 pathway.
abstract: BACKGROUND
  IL-1β has been shown to play a pivotal role in autoimmunity. Cysteinyl aspartate-specific proteinase-1 (caspase-1) inhibitor may be an important drug target for autoimmune diseases. However, the effects of caspase-1 inhibitor on myasthenia gravis (MG) remain undefined.
  
  
  METHODS
  To investigate the effects of caspase-1 inhibitor on experimental autoimmune myasthenia gravis (EAMG), an animal model of MG, caspase-1 inhibitor was administered to Lewis rats immunized with region 97-116 of the rat AChR α subunit (R97-116 peptide) in complete Freund's adjuvant. The immunophenotypical characterization by flow cytometry and the levels of autoantibody by ELISA were carried out to evaluate the neuroprotective effect of caspase-1 inhibitor.
  
  
  RESULTS
  We found that caspase-1 inhibitor improved EAMG clinical symptom, which was associated with decreased IL-17 production by CD4+ T cells and γδ T cells, lower affinity of anti-R97-116 peptide IgG. Caspase-1 inhibitor decreased expression of CD80, CD86, and MHC class II on DCs, as well as intracellular IL-1β production from DCs. In addition, caspase-1 inhibitor treatment inhibited R97-116 peptide-specific cell proliferation and decreased follicular helper T cells relating to EAMG development.
  
  
  CONCLUSIONS
  Our results suggest that caspase-1 inhibitor ameliorates experimental autoimmune myasthenia gravis by innate DC IL-1-IL-17 pathway and provides new evidence that caspase-1 is an important drug target in the treatment of MG and other autoimmune diseases.
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, China. skyfly_32633@126.com.
authors.forename: Cong-Cong
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, China. liheng_sdu@163.com.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, China. zhangmin19870823@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, China. li2006xl@163.com.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Li
authors.affiliation: Central Laboratory, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, China. yuelongtao864@163.com.
authors.forename: Long-Tao
authors.initials: LT
authors.lastname: Yue
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, China. 18305418918@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, China. zhaoyueslim@hotmail.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, China. ab0782@sina.com.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, 250012, China. nancyduan94@hotmail.com.
authors.forename: Ruo-Nan
authors.initials: RN
authors.lastname: Duan
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, China. Liyanbin@sdhospital.com.cn.
authors.forename: Yan-Bin
authors.initials: YB
authors.lastname: Li
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, China. ruisheng_duan@yahoo.com.
authors.forename: Rui-Sheng
authors.initials: RS
authors.lastname: Duan
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D020170:Caspase 1; D061945:Caspase Inhibitors / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D007375:Interleukin-1; D020381:Interleukin-17; D008214:Lymphocytes / Q000473:pathology; D009000:Monocytes / Q000473:pathology; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000188:drug therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D001323:Autoantibodies; D061945:Caspase Inhibitors; D016207:Cytokines; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D020381:Interleukin-17; D011950:Receptors, Cholinergic; D020170:Caspase 1