Fingolimod Immune Effects Beyond Its Sequestration Ability

Research output: Contribution to journalReview article

Abstract

Fingolimod is the first orally administered drug approved for the treatment of relapsing-remitting multiple sclerosis (MS). This drug, modulating sphingosine receptors, regulates the trafficking of lymphocytes between primary and secondary lymphoid organs, trapping naïve T cells and central memory T cells in secondary lymphoid organs, without affecting effector memory T cells and therefore without compromising immunosurveillance. Additionally, fingolimod inhibits expression of Th1 and Th17 cytokines and enhances regulatory T-cell differentiation. It also acts on the B arm of immunity through an increased ratio of naïve to memory B cells, higher percentage of plasma cells, and highly increased proportion of transitional B cells as well as additional regulatory subsets. Fingolimod treatment enhances the capacity of regulatory B cells to transmigrate across brain endothelial cells. In fact, patients treated with fingolimod have increased regulatory B-cell frequency in the cerebrospinal fluid. These findings suggest a novel role for fingolimod in MS, by both direct effects and indirect partitioning effects on lymphocytes.

Original languageEnglish
Pages (from-to)231-240
Number of pages10
JournalNeurology and Therapy
Volume8
Issue number2
DOIs
Publication statusPublished - Dec 2019

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