Inhibition of the BMP Signaling Pathway Ameliorated Established Clinical Symptoms of Experimental Autoimmune Encephalomyelitis

Autor: Vanessa Gil, Carme Martínez Costa, José Antonio del Río, Gemma Reverter-Vives, Herena Eixarch, Xavier Montalban, Carmen Espejo, Mireia Castillo, Laura Calvo-Barreiro
Rok vydání: 2020
Předmět:
Zdroj: Neurotherapeutics
ISSN: 1878-7479
1933-7213
DOI: 10.1007/s13311-020-00885-8
Popis: Bone morphogenetic proteins (BMPs) are secreted growth factors that belong to the transforming growth factor beta superfamily. BMPs have been implicated in physiological processes, but they are also involved in many pathological conditions. Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS); however, its etiology remains elusive. Some evidence points to BMPs as important players in the pathogenesis of inflammatory and autoimmune disorders. In the present work, we studied the expression of BMP2, BMP4, BMP5, BMP6, BMP7, BMP type II receptor, and noggin in the immune system during different phases of experimental autoimmune encephalomyelitis (EAE). Major changes in the expression of BMPs took place in the initial phases of EAE. Indeed, those changes mainly affected BMP6 (whose expression was abrogated), BMP2, and BMP7 (whose expression was increased). In addition, we showed that in vivo inhibition of the BMP signaling pathway with small molecules ameliorated the already established clinical symptoms of EAE, as well as the CNS histopathological features. At the immune level, we observed an expansion of plasmacytoid dendritic cells (pDCs) in mice treated with small molecules that inhibit the BMP signaling pathway. pDCs could play an important role in promoting the expansion of antigen-specific regulatory T cells. Altogether, our data suggest a role for BMPs in early immune events that take place in myelin oligodendrocyte glycoprotein (MOG)-induced EAE. In addition, the clinical outcome of the disease was improved when the BMP signaling pathway was inhibited in mice that presented established EAE symptoms. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00885-8) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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