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Platelets play differential role during the initiation and progression of autoimmune neuroinflammation

Item Type:Article
Title:Platelets play differential role during the initiation and progression of autoimmune neuroinflammation
Creators Name:Starossom, S.C. and Veremeyko, T. and Yung, A.W.Y. and Dukhinova, M. and Au, C. and Lau, A.Y. and Weiner, H.L. and Ponomarev, E.D.
Abstract:RATIONALE: 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. METHODS AND 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. CONCLUSION: 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.
Keywords:Blood Platelets, Interleukin-17, Multiple Sclerosis, Serotonin, T-lymphocytes, Helper-inducer, Animals, Mice
Source:Circulation Research
Publisher:American Heart Association
Page Range:779-792
Date:9 October 2015
Additional Information:Copyright © 2015 American Heart Association, Inc.
Official Publication:https://doi.org/10.1161/circresaha.115.306847
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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