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.

骨形态发生蛋白 (BMP) 是属于转化生长因子 β 超家族的分泌生长因子。BMP 与生理过程有关，但它们也与许多病理状况有关。多发性硬化症 (MS) 是一种免疫介导的中枢神经系统 (CNS) 疾病；然而，它的病因仍然难以捉摸。一些证据表明 BMP 是炎症和自身免疫性疾病发病机制中的重要参与者。在目前的工作中，我们研究了实验性自身免疫性脑脊髓炎 (EAE) 不同阶段免疫系统中 BMP2、BMP4、BMP5、BMP6、BMP7、BMP II 型受体和头蛋白的表达。BMPs 表达的主要变化发生在 EAE 的初始阶段。事实上，这些变化主要影响 BMP6（其表达被废除）、BMP2、和 BMP7（其表达增加）。此外，我们证明了用小分子在体内抑制 BMP 信号通路改善了已经确定的 EAE 临床症状以及 CNS 组织病理学特征。在免疫水平上，我们观察到用抑制 BMP 信号通路的小分子处理的小鼠中浆细胞样树突状细胞 (pDC) 的扩增。pDCs 可以在促进抗原特异性调节性 T 细胞的扩增中发挥重要作用。总之，我们的数据表明 BMP 在髓鞘少突胶质细胞糖蛋白 (MOG) 诱导的 EAE 中发生的早期免疫事件中的作用。此外，当在出现 EAE 症状的小鼠中抑制 BMP 信号通路时，该疾病的临床结果得到改善。