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

• Published in: Neurotherapeutics Vol. 17; no. 4; pp. 1988 - 2003
• Main Authors: Eixarch, Herena, Calvo-Barreiro, Laura, Costa, Carme, Reverter-Vives, Gemma, Castillo, Mireia, Gil, Vanessa, Del Río, José Antonio, Montalban, Xavier, Espejo, Carmen
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-10-2020; Springer Nature B.V
• Subjects: Animals; Autoimmune diseases; Biomedical and Life Sciences; Biomedicine; Bone morphogenetic protein 2; Bone morphogenetic protein 4; Bone Morphogenetic Protein 4 - antagonists & inhibitors; Bone Morphogenetic Protein 4 - metabolism; Bone morphogenetic protein 5; Bone morphogenetic protein 6; Bone morphogenetic protein 7; Bone morphogenetic proteins; Bone Morphogenetic Proteins - antagonists & inhibitors; Bone Morphogenetic Proteins - metabolism; Carrier Proteins - administration & dosage; Central nervous system; Dendritic cells; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - metabolism; Etiology; Experimental allergic encephalomyelitis; Female; Humans; Immune system; Immunoregulation; Jurkat Cells; Kinases; Lymphocytes T; Mice; Mice, Inbred C57BL; Multiple sclerosis; Myelin; Neurobiology; Neurology; Neurosciences; Neurosurgery; Noggin protein; Oligodendrocyte-myelin glycoprotein; Original; Original Article; Pyrazoles - administration & dosage; Quinolines - administration & dosage; Signal transduction; Signal Transduction - drug effects; Signal Transduction - physiology; Transforming growth factor-b; Dorsomorphin; Experimental autoimmune encephalomyelitis; Multiple sclerosis; DMH1; Bone morphogenetic protein; Immune response
• ISSN: 1933-7213; 1878-7479; 1878-7479
• DOI: 10.1007/s13311-020-00885-8

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.