The Role of platelet-T cell interactions in pathogenesis of Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO)
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AbstractIntroduction and Project Objectives:
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. The main objective of the study was to understand the role of platelets in modulation of functions of pathogenic CD4 T cells in MS.
Methods/Implementation:
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 (EAE), an animal model for MS.
Results/Outcome:
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.
Acceptance Date11/06/2019
All Author(s) ListStarossom S, Veremeyko T, Dukhinova M, Yung AWY, Lau AY, Au C, Ponomarev ED
Name of ConferenceHealth Research Symposium 2019
Start Date of Conference12/06/2019
End Date of Conference12/06/2019
Place of ConferenceHong Kong Academy of Medicine Jockey Club Building
Country/Region of ConferenceHong Kong
Year2019
Month6
LanguagesEnglish-United Kingdom
KeywordsPlatelets, Multiple Sclerosis, brain lipid rafts, EAE

Last updated on 2019-20-06 at 12:13