![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
| Item Type: | Article |
|---|---|
| Title: | Platelets play differential role during the initiation and progression of autoimmune neuroinflammation |
| Creators Name: | Starossom, S.C., Veremeyko, T., Yung, A.W.Y., Dukhinova, M., Au, C., Lau, A.Y., 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 |
| ISSN: | 0009-7330 |
| Publisher: | American Heart Association |
| Volume: | 117 |
| Number: | 9 |
| 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 |
Repository Staff Only: item control page
