Suchergebnisse

The most frequent variant of multiple sclerosis (MS) is the relapsing-remitting form, characterized by symptomatic phases followed by periods of total/partial recovery. Hence, it is possible that these patients can benefit from endogenous agents that control the inflammatory process and favor spontaneous remyelination. In this context, there is increasing interest in the role of myeloid-derived suppressor cells (MDSCs) during the clinical course of experimental autoimmune encephalomyelitis (EAE). MDSCs speed up infiltrated T-cell anergy and apoptosis. In different animal models of MS, a milder disease course is related to higher presence/density of MDSCs in the periphery, and smaller demyelinated lesions in the central nervous system (CNS). These observations lead us to wonder whether MDSCs might not only exert an anti-inflammatory effect but might also have direct influence on oligodendrocyte precursor cells (OPCs) and remyelination. In the present work, we reveal for the first time the relationship between OPCs and MDSCs in EAE, relationship that is guided by the distance from the inflammatory core. We describe the effects of MDSCs on survival, proliferation, as well as potent promoters of OPC differentiation toward mature phenotypes. We show for the first time that osteopontin is remarkably present in the analyzed secretome of MDSCs. The ablation of this cue from MDSCs-secretome demonstrates that osteopontin is the main MDSC effector on these oligodendroglial cells. These data highlight a crucial pathogenic interaction between innate immunity and the CNS, opening ways to develop MDSC- and/or osteopontin-based therapies to promote effective myelin preservation and repair in MS patients. ; This work was supported by the Spanish Ministerio de Economía, Industria y Competitividad-MINEICO (currently Ministerio de Ciencia e Innovación: grants SAF2012-40023, SAF2015-72325-EXP, SAF2016-77575-R, and PID2019-109858RB-I00); the Instituto de Salud Carlos III (grants RD12-0032-12, RD16-0015-0019, PI15-00963, and PI18-00357—partially financed by F.E.D.E.R.: European Union "Una manera de hacer Europa"-); the Spanish Research Council/Consejo Superior de Investigaciones Científicas-CSIC (grants CSIC-2015201023, 2019AEP033, and LINKA20268); and ADEM-TO (Spain), ATORDEM (Spain), AELEM (Spain), and ARSEP Foundations (France). D. C. and R. L. G. were financed by SESCAM. C. M.-J. held a BES-2013-062630 predoctoral Research Training contract from MINEICO (associated with SAF2012-40023 and PI15-00963) and a contract under SAF2015-72325-EXP and SAF2016-77575-R. B. F.-G. is currently contracted under IND2018/BMD-9751 (Comunidad de Madrid, Spain). M. C. O holds a postdoctoral contract from the Consejería de Sanidad de Castilla-La Mancha (II-2018_07). Dr Clemente's group was sponsored by Aciturri Aeronáutica SLA, Fundación Galletas Coral, and Embutidos y Jamones España e Hijos.