P-Glycoprotein Acts as an Immunomodulator during Neuroinflammation

• DOI: 10.1371/journal.pone.0008212
• Publication Date: 2009-12-08T03:33:19Z
• Authors: Gijs Kooij; Ronald Backer; Jasper J. Koning; Arie Reijerkerk; Jack van Horssen; Susanne M. A. van...; Joost Drexhage; Alfred Schinkel; Christine D. Dijk...; Joke M. M. den Haan; Teunis B. H. Geij...; Helga E. de Vries
• Keywords: Myelin oligodendrocyte glycoprotein; Encephalomyelitis

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system in which autoreactive myelin-specific T cells cause extensive tissue damage, resulting neurological deficits. In process, are primed periphery by antigen presenting dendritic (DCs). DCs considered to be crucial regulators specific immune responses and molecules or proteins that regulate DC function therefore under investigation. We here investigated potential immunomodulatory capacity ATP binding cassette transporter P-glycoprotein (P-gp). P-gp generally drives cellular efflux a variety compounds thought involved excretion agents from cells, like DCs. So far, role these ABC transporters unknown.Here we demonstrate acts as key modulator adaptive immunity during vivo model for neuroinflammation. The severely impaired knockout mice (Mdr1a/1b-/-), since both maturation cell stimulatory significantly decreased. Consequently, Mdr1a/1b -/- develop decreased clinical signs experimental autoimmune encephalomyelitis (EAE), animal multiple sclerosis. Reduced coincided with cell-specific brain inflammation. describe underlying molecular mechanism secretion pro-inflammatory cytokines such TNF-alpha IFN-gamma. Importantly, defect can restored exogenous addition cytokines.Our data downmodulates through regulation cytokine secretion, response. Taken together, our work highlights new physiological molecule reveals possible target immunotherapy.