title: Recombinant human PDCD5 (rhPDCD5) protein is protective in a mouse model of multiple sclerosis.
abstract: BACKGROUND
  In multiple sclerosis (MS) and its widely used animal model, experimental autoimmune encephalomyelitis (EAE), autoreactive T cells contribute importantly to central nervous system (CNS) tissue damage and disease progression. Promoting apoptosis of autoreactive T cells may help eliminate cells responsible for inflammation and may delay disease progression and decrease the frequency and severity of relapse. Programmed cell death 5 (PDCD5) is a protein known to accelerate apoptosis in response to various stimuli. However, the effects of recombinant human PDCD5 (rhPDCD5) on encephalitogenic T cell-mediated inflammation remain unknown.
  
  
  METHODS
  We examined the effects of intraperitoneal injection of rhPDCD5 (10 mg/kg) on EAE both prophylactically (started on day 0 post-EAE induction) and therapeutically (started on the onset of EAE disease at day 8), with both of the treatment paradigms being given every other day until day 25. Repeated measures two-way analysis of variance was used for statistical analysis.
  
  
  RESULTS
  We showed that the anti-inflammatory effects of rhPDCD5 were due to a decrease in Th1/Th17 cell frequency, accompanied by a reduction of proinflammatory cytokines, including IFN-γ and IL-17A, and were observed in both prophylactic and therapeutic regimens of rhPDCD5 treatment in EAE mice. Moreover, rhPDCD5-induced apoptosis of myelin-reactive CD4+ T cells, along with the upregulation of Bax and downregulation of Bcl-2, and with activated caspase 3.
  
  
  CONCLUSIONS
  Our data demonstrate that rhPDCD5 ameliorates the autoimmune CNS disease by inhibiting Th1/Th17 differentiation and inducing apoptosis of predominantly pathogenic T cells. This study provides a novel mechanism to explain the effects of rhPDCD5 on neural inflammation. The work represents a translational demonstration that rhPDCD5 has prophylactic and therapeutic properties in a model of multiple sclerosis.
authors.affiliation: Medical College, Hubei University of Arts and Science, Xiangyang, 441053, China. ju_126@126.com.|Department of Immunology, Peking University School of Basic Medical Sciences, Peking University Center for Human Disease Genomics, 38 Xueyuan Road, Beijing, 100191, China. ju_126@126.com.|Department of Biochemistry and Molecular Medicine, School of Medicine, University of California-Davis, 2425 Stockton Boulevard, Sacramento, CA, 95817, USA. ju_126@126.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Medical College, Hubei University of Arts and Science, Xiangyang, 441053, China. liuwenwei@medmail.com.cn.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Immunology, Peking University School of Basic Medical Sciences, Peking University Center for Human Disease Genomics, 38 Xueyuan Road, Beijing, 100191, China. yingyu_chen@bjmu.edu.cn.
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Medical College, Hubei University of Arts and Science, Xiangyang, 441053, China. wbdeng@ucdavis.edu.|Department of Biochemistry and Molecular Medicine, School of Medicine, University of California-Davis, 2425 Stockton Boulevard, Sacramento, CA, 95817, USA. wbdeng@ucdavis.edu.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Deng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D053148:Caspase 3 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology; D009363:Neoplasm Proteins / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000627:therapeutic use; D013116:Spinal Cord / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology; D018417:Th1 Cells / Q000473:pathology; D058504:Th17 Cells / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D009363:Neoplasm Proteins; D018696:Neuroprotective Agents; C117283:PDCD5 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D053148:Caspase 3