Myeloid cells as target of fingolimod action in multiple sclerosis

Marco Di Dario, Emanuela Colombo, Chiara Govi, Donatella De Feo, Maria José Messina, Marzia Romeo, Francesca Sangalli, Lucia Moiola, Mariaemma Rodegher, Gianvito Martino, Vittorio Martinelli, Giancarlo Comi, Cinthia Farina

Research output: Contribution to journalArticle

Abstract

Objective: To track the effects of fingolimod, an approved drug for multiple sclerosis (MS), on the activation of myeloid cells from the periphery to the CNS. Methods: In vitro and ex vivo immunologic studies coupled with flow cytometry were performed to evaluate the action of fingolimod on lipopolysaccharide (LPS)-induced expression of activation markers in human monocytes from healthy participants, participants with untreated MS, and participants with fingolimod-treated MS. In vivo administration of fingolimod during experimental autoimmune encephalomyelitis (EAE) was established to verify the activation state of splenic, CNS infiltrating, and CNS resident myeloid cells ex vivo at flow cytometer. Results: We found that in vitro exposure of human monocytes to fingolimod inhibited LPS-induced CD25 and CD150 expression and tumor necrosis factor-α (TNF-α) secretion without altering immune cell survival. Further, EAE treatment with fingolimod led to reduced amounts of TNF-α produced by myeloid cells in vivo in the spleen and CNS. Finally, while displaying normal induction of CD25 and CD150 levels at high LPS concentration, monocytes from patients with fingolimodtreated MS showed significantly higher activation threshold at suboptimal LPS stimulation than controls. Conclusions: The inhibition of myeloid cell activation may be part of the immunosuppressive action of fingolimod and take place in the periphery and in the CNS.

Original languageEnglish
Article numbere157
JournalNeurology
Volume2
Issue number6
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Clinical Neurology

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    Di Dario, M., Colombo, E., Govi, C., De Feo, D., Messina, M. J., Romeo, M., Sangalli, F., Moiola, L., Rodegher, M., Martino, G., Martinelli, V., Comi, G., & Farina, C. (2015). Myeloid cells as target of fingolimod action in multiple sclerosis. Neurology, 2(6), [e157]. https://doi.org/10.1212/NXI.0000000000000157