Mansilla María José, Sellès-Moreno Carla, Fàbregas-Puig Sara, Amoedo Joan, Navarro-Barriuso Juan, Teniente-Serra Aina, Grau-López Laia, Ramo-Tello Cristina, Martínez-Cáceres Eva M
Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti, Badalona, Spain; Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
CNS Neurosci Ther. 2015 Mar;21(3):222-30. doi: 10.1111/cns.12342. Epub 2014 Nov 18.
Treatment with tolerogenic dendritic cells (TolDC) is a promising, cell-based strategy to regulate autoimmune diseases such as multiple sclerosis (MS) in an antigen-specific way. This technique involves the use of TolDC from MS patients cultured in the presence of vitamin D(3) (VitD3) and pulsed with myelin peptides to induce a stable hyporesponsiveness in myelin-specific autologous T cells.
The purpose of this study was to analyze the in vivo effect of VitD3-TolDC treatment on experimental autoimmune encephalomyelitis, an animal model of MS.
Bone marrow-derived TolDC cultured in the presence of VitD3 and pulsed with peptide 40-55 of the myelin oligodendrocyte glycoprotein (MOG(40-55)) were administrated preventively, preclinically, and therapeutically to EAE-induced mice.
We found that VitD3-TolDC-MOG treatment showed a beneficial effect, not only decreasing the incidence of the disease but also reducing the severity of the clinical signs mediated by induction of regulatory T cells (Treg), as well as IL-10 production and reduction of Ag-specific lymphoproliferation. Our results support VitD3-TolDC-peptide(s) treatment as a potential strategy to restore tolerance in autoimmune diseases such as MS.
用耐受性树突状细胞(TolDC)进行治疗是一种有前景的基于细胞的策略,可通过抗原特异性方式调节自身免疫性疾病,如多发性硬化症(MS)。该技术涉及使用来自MS患者的TolDC,在维生素D3(VitD3)存在下培养并用髓鞘肽脉冲处理,以诱导髓鞘特异性自体T细胞产生稳定的低反应性。
本研究的目的是分析VitD3-TolDC治疗对实验性自身免疫性脑脊髓炎(一种MS动物模型)的体内效应。
将在VitD3存在下培养并用髓鞘少突胶质细胞糖蛋白(MOG(40-55))的40-55肽脉冲处理的骨髓来源的TolDC预防性、临床前和治疗性地给予EAE诱导的小鼠。
我们发现VitD3-TolDC-MOG治疗显示出有益效果,不仅降低了疾病的发生率,还通过诱导调节性T细胞(Treg)以及IL-10的产生和Ag特异性淋巴细胞增殖的减少减轻了临床症状的严重程度。我们的结果支持VitD3-TolDC-肽治疗作为恢复MS等自身免疫性疾病耐受性的潜在策略。