{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:04:40Z","timestamp":1792598680970,"version":"4.5.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2015,10,9]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>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-\u03b3\/interleukin-17\u2013producing 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\u2013CD4 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-\u03b3. Blocking of formation of platelet\u2013CD4 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusion<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.115.306847","type":"journal-article","created":{"date-parts":[[2015,10,8]],"date-time":"2015-10-08T20:43:07Z","timestamp":1444336987000},"page":"779-792","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":88,"title":["Platelets Play Differential Role During the Initiation and Progression of Autoimmune Neuroinflammation"],"prefix":"10.1161","volume":"117","author":[{"given":"Sarah C.","family":"Starossom","sequence":"first","affiliation":[{"name":"From the Center for Neurologic Diseases, Brigham and Women\u2019s 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, Charit\u00e9 - Universit\u00e4tsmedizin 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Veremeyko","sequence":"additional","affiliation":[{"name":"From the Center for Neurologic Diseases, Brigham and Women\u2019s 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, Charit\u00e9 - Universit\u00e4tsmedizin 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda W.Y.","family":"Yung","sequence":"additional","affiliation":[{"name":"From the Center for Neurologic Diseases, Brigham and Women\u2019s 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, Charit\u00e9 - Universit\u00e4tsmedizin 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Dukhinova","sequence":"additional","affiliation":[{"name":"From the Center for Neurologic Diseases, Brigham and Women\u2019s 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, Charit\u00e9 - Universit\u00e4tsmedizin 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Au","sequence":"additional","affiliation":[{"name":"From the Center for Neurologic Diseases, Brigham and Women\u2019s 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, Charit\u00e9 - Universit\u00e4tsmedizin 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Y.","family":"Lau","sequence":"additional","affiliation":[{"name":"From the Center for Neurologic Diseases, Brigham and Women\u2019s 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, Charit\u00e9 - Universit\u00e4tsmedizin 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard L.","family":"Weiner","sequence":"additional","affiliation":[{"name":"From the Center for Neurologic Diseases, Brigham and Women\u2019s 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, Charit\u00e9 - Universit\u00e4tsmedizin 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene D.","family":"Ponomarev","sequence":"additional","affiliation":[{"name":"From the Center for Neurologic Diseases, Brigham and Women\u2019s 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, Charit\u00e9 - Universit\u00e4tsmedizin 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH13-09-0805"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2012.751534"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-7-10"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm810"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2140"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1780"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1181928"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2956"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1251502"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0213074"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2011.10.010"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH11-01-0020"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12612"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.1.39"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2031"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203172"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61620-7"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.14"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.269050"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096256"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(65)90069-3"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.02147.x"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-5-27"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0502-500"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.256370"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058979"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1191\/1352458503ms965oa"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2010.08.011"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081774"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.3791\/4097"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900568"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2266"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20488"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(00)00256-X"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1006\/cbir.1999.0426"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2885.2008.00944.x"},{"key":"e_1_3_4_38_2","first-page":"25","article-title":"[A chronic fatigue syndrome and blood platelet serotonin levels in patients with multiple sclerosis.].","volume":"114","author":"Ba\u012ddina TV","year":"2014","unstructured":"Ba\u012ddina TV, Akintseva IV, Trushnikova TN. 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