The presence and suppressive activity of myeloid-derived suppressor cells are potentiated after interferon-β treatment in a murine model of multiple sclerosis

Autor: Rafael Lebrón-Galán, Fernando de Castro, Margarita Suardíaz, Oscar Fernandez, Carolina Melero-Jerez, Isabel Machín-Díaz, Begoña Oliver-Martos, Diego Clemente, Carmen Marín-Bañasco
Přispěvatelé: Ministerio de Economía, Industria y Competitividad (España), Federación Española de Enfermedades Raras, Consejo Superior de Investigaciones Científicas (España), Fondation pour l'aide à la recherche sur la sclérose en plaques, Fundación Sociosanitaria de Castilla-La Mancha
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Neurobiology of Disease, Vol 127, Iss, Pp 13-31 (2019)
Digital.CSIC. Repositorio Institucional del CSIC
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Popis: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the human central nervous system (CNS), mainly affecting young adults. Among the immunomodulatory disease modifying treatments approved up to date to treat MS, IFN-β remains to be one of the most widely prescribed for the Relapsing-Remitting (RR) variant of the disease, although its mechanism of action is still partially understood. RR-MS variant is characterized by phases with increasing neurological symptoms (relapses) followed by periods of total or partial recovery (remissions), which implies the existence of immunomodulatory agents to promote the relapsing-to-remitting transition. Among these agents, it has been described the immunosuppressive role of a heterogeneous population of immature myeloid cells, namely the myeloid-derived suppressor cells (MDSCs) during the clinical course of the experimental autoimmune encephalomyelitis (EAE), the most used MS model to study RRMS. However, it is still unknown how the current MS disease modifying treatments, e.g. IFN- β, affects to MDSCs number or activity. Our present results show that a single injection of IFN-β at the onset of the clinical course reduces the severity of the EAE, enhancing the presence of MDSCs within the smaller demyelinated areas. Moreover, the single dose of IFN-β promotes MDSC immunosuppressive activity both in vivo and in vitro, augmenting T cell apoptosis. Finally, we show that IFN-ß preserves MDSC immaturity, preventing their differentiation to mature and less suppressive myeloid cell subsets. Taking together, all these data add new insights into the mechanism of IFN-β treatment in EAE and point to MDSCs as a putative endogenous mediator of its beneficial role in this animal model of MS.
This work was supported by the Spanish Ministerio de Economía, Industria y Competitividad-MINEICO (SAF2012-40023; SAF2016-77575-R; RD12-0032-12; RD16-0015-0019; PI15-00963; 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 (CSIC-2015201023), ADEM-TO (Spain) and ARSEP Foundation (France). DC, RL-G and IM-D were financed by SESCAM; CM-J holds a predoctoral Research Training contract from MINEICO (BES-2013-062630, –associated to SAF2012-40023 and PI15-00963) and is currently hired under SAF2016-77577-R. Dr. Clemente's group was sponsored by Aciturri Aeronáutica SLU, Vesuvius Ibérica LA and Fundación Galletas Coral.
Databáze: OpenAIRE
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