title: Platelets Play Differential Role During the Initiation and Progression of Autoimmune Neuroinflammation.
abstract: BACKGROUND
  Platelets are known to participate in vascular pathologies; however, their role in neuroinflammatory diseases, such as multiple sclerosis (MS), is unknown. Autoimmune CD4 T cells have been the main focus of studies of MS, although the factors that regulate T-cell differentiation toward pathogenic T helper-1/T helper-17 phenotypes are not completely understood.
  
  
  OBJECTIVE
  We investigated the role of platelets in the modulation of CD4 T-cell functions in patients with MS and in mice with experimental autoimmune encephalitis, an animal model for MS.
  
  
  RESULTS
  We found that early in MS and experimental autoimmune encephalitis, platelets degranulated and produced soluble factors serotonin (5-hydroxytryptamine), platelet factor 4, and platelet-activating factor, which specifically stimulated differentiation of T cells toward pathogenic T helper-1, T helper-17, and interferon-γ/interleukin-17-producing CD4 T cells. At the later stages of MS and experimental autoimmune encephalitis, platelets became exhausted in their ability to produce proinflammatory factors and stimulate CD4 T cells but substantially increased their ability to form aggregates with CD4 T cells. Formation of platelet-CD4 T-cell aggregates involved the interaction of CD62P on activated platelets with adhesion molecule CD166 on activated CD4 T cells, contributing to downmodulation of CD4 T-cell activation, proliferation, and production of interferon-γ. Blocking of formation of platelet-CD4 T-cell aggregates during progression of experimental autoimmune encephalitis substantially enhanced proliferation of CD4 T cells in the central nervous system and the periphery leading to exacerbation of the disease.
  
  
  CONCLUSIONS
  Our study indicates differential roles for platelets in the regulation of functions of pathogenic CD4 T cells during initiation and progression of central nervous system autoimmune inflammation.
authors: From the Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA (S.C.S., H.L.W., E.D.P.); Institute for Medical Immunology and NeuroCure, Department of Experimental Neuroimmunology, Charité - Universitätsmedizin Berlin, Berlin, Germany (S.C.S.); and School of Biomedical Sciences, Faculty of Medicine (T.V., A.W.Y.Y., M.D., E.D.P.) and Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital (C.A., A.Y.L.), The Chinese University of Hong Kong, Hong Kong.
authors: Sarah C
authors: SC
authors: Starossom
authors: From the Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA (S.C.S., H.L.W., E.D.P.); Institute for Medical Immunology and NeuroCure, Department of Experimental Neuroimmunology, Charité - Universitätsmedizin Berlin, Berlin, Germany (S.C.S.); and School of Biomedical Sciences, Faculty of Medicine (T.V., A.W.Y.Y., M.D., E.D.P.) and Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital (C.A., A.Y.L.), The Chinese University of Hong Kong, Hong Kong.
authors: Tatyana
authors: T
authors: Veremeyko
authors: From the Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA (S.C.S., H.L.W., E.D.P.); Institute for Medical Immunology and NeuroCure, Department of Experimental Neuroimmunology, Charité - Universitätsmedizin Berlin, Berlin, Germany (S.C.S.); and School of Biomedical Sciences, Faculty of Medicine (T.V., A.W.Y.Y., M.D., E.D.P.) and Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital (C.A., A.Y.L.), The Chinese University of Hong Kong, Hong Kong.
authors: Amanda W Y
authors: AW
authors: Yung
authors: From the Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA (S.C.S., H.L.W., E.D.P.); Institute for Medical Immunology and NeuroCure, Department of Experimental Neuroimmunology, Charité - Universitätsmedizin Berlin, Berlin, Germany (S.C.S.); and School of Biomedical Sciences, Faculty of Medicine (T.V., A.W.Y.Y., M.D., E.D.P.) and Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital (C.A., A.Y.L.), The Chinese University of Hong Kong, Hong Kong.
authors: Marina
authors: M
authors: Dukhinova
authors: From the Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA (S.C.S., H.L.W., E.D.P.); Institute for Medical Immunology and NeuroCure, Department of Experimental Neuroimmunology, Charité - Universitätsmedizin Berlin, Berlin, Germany (S.C.S.); and School of Biomedical Sciences, Faculty of Medicine (T.V., A.W.Y.Y., M.D., E.D.P.) and Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital (C.A., A.Y.L.), The Chinese University of Hong Kong, Hong Kong.
authors: Cheryl
authors: C
authors: Au
authors: From the Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA (S.C.S., H.L.W., E.D.P.); Institute for Medical Immunology and NeuroCure, Department of Experimental Neuroimmunology, Charité - Universitätsmedizin Berlin, Berlin, Germany (S.C.S.); and School of Biomedical Sciences, Faculty of Medicine (T.V., A.W.Y.Y., M.D., E.D.P.) and Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital (C.A., A.Y.L.), The Chinese University of Hong Kong, Hong Kong.
authors: Alexander Y
authors: AY
authors: Lau
authors: From the Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA (S.C.S., H.L.W., E.D.P.); Institute for Medical Immunology and NeuroCure, Department of Experimental Neuroimmunology, Charité - Universitätsmedizin Berlin, Berlin, Germany (S.C.S.); and School of Biomedical Sciences, Faculty of Medicine (T.V., A.W.Y.Y., M.D., E.D.P.) and Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital (C.A., A.Y.L.), The Chinese University of Hong Kong, Hong Kong.
authors: Howard L
authors: HL
authors: Weiner
authors: From the Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA (S.C.S., H.L.W., E.D.P.); Institute for Medical Immunology and NeuroCure, Department of Experimental Neuroimmunology, Charité - Universitätsmedizin Berlin, Berlin, Germany (S.C.S.); and School of Biomedical Sciences, Faculty of Medicine (T.V., A.W.Y.Y., M.D., E.D.P.) and Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital (C.A., A.Y.L.), The Chinese University of Hong Kong, Hong Kong. eponomarev@cuhk.edu.hk.
authors: Eugene D
authors: ED
authors: Ponomarev
mesh_terms: D000328:Adult; D000818:Animals; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D010972:Platelet Activating Factor / Q000276:immunology / Q000378:metabolism; D010978:Platelet Factor 4 / Q000276:immunology / Q000378:metabolism; D012701:Serotonin / Q000276:immunology / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D010972:Platelet Activating Factor; D012701:Serotonin; D010978:Platelet Factor 4; D007371:Interferon-gamma
keywords: T-lymphocytes; blood platelets; helper-inducer; interleukin-17; multiple sclerosis; serotonin