title: Differential effects of ponesimod, a selective S1P1 receptor modulator, on blood-circulating human T cell subpopulations.
abstract: Ponesimod, a novel selective sphingosine-1-phosphate 1 receptor modulator in the development for the treatment of autoimmune diseases, dose-dependently reduced lymphocyte counts in peripheral blood of healthy subjects. It rapidly and transiently reduced the number of circulating T and B cells, but not natural killer cells. T lymphocyte subsets exhibited differential sensitivities with a maximum decrease from baseline ranging from 67% to 89% following high doses. Naïve T cells were more sensitive than memory T cells. CD4(+) T cells were more sensitive than CD8(+) T cells or CD4(+)CD25(+) T regulatory cells. The differential effects on specialized T cell subsets may contribute to the immunomodulatory activity of ponesimod. The therapeutic potential of ponesimod has been recently shown in phase II studies of chronic plaque psoriasis and relapsing-remitting multiple sclerosis. Our data suggest that lymphocyte sequestration underlies the therapeutic potential of ponesimod in multiple autoimmune and chronic inflammatory diseases.
authors.affiliation: Department of Global Clinical Science & Epidemiology, Actelion Pharmaceuticals Ltd , Allschwil , Switzerland .
authors.forename: Daniele
authors.initials: D
authors.lastname: D'Ambrosio
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinmann
authors.forename: Patrick
authors.initials: P
authors.lastname: Brossard
authors.forename: Jasper
authors.initials: J
authors.lastname: Dingemanse
mesh_terms: D018951:Antigens, CD20 / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D017252:CD3 Complex / Q000096:biosynthesis / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000276:immunology; D064368:Healthy Volunteers; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D017452:Receptors, IgG / Q000096:biosynthesis / Q000276:immunology; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D013844:Thiazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D018951:Antigens, CD20; D017252:CD3 Complex; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG; D049349:Receptors, Lysosphingolipid; D013844:Thiazoles; C550169:ponesimod
keywords: Cell migration; immune response; lymphocyte subsets; lymphocyte trafficking; sphingosine 1 phosphate receptor