Increased understanding of the role of sphingosine-1-phosphate (SIP) in modulating the circulation of T lymphocytes has led to development of a new class of targeted therapies for psoriasis.1 In The Lancet, Andrea Vaclavkova and colleagues2 report on a phase 2 study of ponesimod, the first oral selective modulator of the SIP receptor 1 (S1PR1), for the treatment of chronic plaque psoriasis. SIP is a lysophospholipid whose activity is mediated through five G-protein-coupled SIP receptors, and ponesimod is a selective S1PR1 antagonist that depletes surface S1PR1 and prevents T-lymphocyte egress from secondary lymphoid tissues into the circulation. Ponesimod and fingoiimod, another antagonist of S1PR1, have successfully been used to treat multiple sclerosis, which is a T-helper-17-mediated inflammatory disease, like psoriasis.
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