Histamine regulates autoreactive T cell activation and adhesiveness in inflamed brain microcirculation

Journal of Leukocyte Biology

Barbara Rossi³  Stefano Angiari³  Marilena Lapilla¹  Gabriela Constantin  and³  Giuseppe Matarese²  Lawrence Steinman⁴  Claudio Procaccini²  Cinthia Farina¹  Marianna Martinello³  Barbara Gallo¹  Massimo Costanza¹  Silvia Musio¹  Rosetta Pedotti¹ 

[1] Neuroimmunology and Neuromuscular Disorders Unit, Neurological Institute Foundation, IRCSS Carlo Besta, Milan, Italy;Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Naples, Italy; Department of Pathology, University of Verona, Verona, Italy;Department of Neurological Sciences and Interdepartmental Program in Immunology, Beckman Center for Molecular Medicine, Stanford University School of Medicine, Stanford, California, USA Neuroimmunology and Neuromuscular Disorders Unit, Neurological Institute Foundation, IRCSS Carlo Besta, Milan, Italy;

关键词: autoimmunity;    EAE;    MS;    cytokine;    chemokine;   

DOI  :  10.1189/jlb.0910486

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Histamine may contribute to the pathology of MS and its animal model EAE. We explored the effects of histamine and specific HR agonists on activation and migratory capacity of myelin-autoreactive T cells. We show that histamine in vitro inhibits proliferation and IFN-γ production of mouse T cells activated against PLP139–151. These effects were mimicked by the H1R agonist HTMT and the H2R agonist dimaprit and were associated with reduced activation of ERK½ kinase and with increased levels of cell cycle inhibitor p27Kip-1, both involved in T cell proliferation and anergy. H1R and H2R agonists reduced spontaneous and chemokine-induced adhesion of autoreactive T cells to ICAM-1 in vitro and blocked firm adhesion of these cells in inflamed brain microcirculation in vivo. Thus histamine, through H1R and H2R, inhibits activation of myelin-autoreactive T cells and their ability to traffic through the inflamed BBB. Strategies aimed at interfering with the histamine axis might have relevance in the therapy of autoimmune disease of the CNS.

【 授权许可】

Unknown