Regulation of EAE by skin immunization with self-peptide

多发性硬化症(MS)是中枢神经系统(CNS)的一种炎症性发作，导致广泛的 脱髓鞘和神经元功能丧失，通常会导致死亡。实验性自身免疫 脑脊髓炎(EAE)是MS的动物模型，本提案将研究免疫的调节 用自身抗原进行皮肤(皮肤)免疫的系统反应。皮下免疫是一种 皮肤斑块浸泡在抗原中的过程，在这种情况下是中枢神经系统抗原髓鞘少突胶质细胞 GylcpProtein(MOG)，在用相同的抗原诱导EAE之前，被应用于小鼠的剃毛皮肤。我们 最近显示，当我们在皮肤表面进行免疫接种或使用MOG进行皮肤贴片时 C57BL/6小鼠在EAE诱导之前，这些小鼠受到保护，不会发生EAE。最重要的是， 当我们在小鼠发生EAE后对它们进行皮肤免疫时，轻度EAE的小鼠就得到了保护， 但不是患有严重EAE的小鼠。我们观察到，受EAE保护的小鼠的CD4T细胞 产生高水平的IL-10，它们可以将保护转移到NAVE受体小鼠。我们还发现， 皮肤中的表皮树突状细胞从贴片中捕获抗原，当它们被 皮下免疫后从皮肤中分离出病毒，并转移到NA受体小鼠体内。的目标是 这项提议有三个具体目标，将决定1)皮肤表面免疫/皮肤 使用MOG贴片可以改善小鼠正在进行的EAE，并减少或防止复发；2)确定 MOG皮下免疫小鼠CD4T细胞介导的耐受依赖于IL-10和IL-3 确定表皮树突状细胞在皮肤免疫诱导耐受中的作用。这些研究 将有助于提高我们对自身免疫性疾病在外周水平和 CNS水平，可能对MS等自身免疫性疾病有一定的治疗作用。

Multiple sclerosis (MS) is an inflammatory attack on the central nervous system (CNS) that results in extensive demyelination and loss of neuronal function that often leads to death. Experimental autoimmune encephalomyelitis (EAE) is the animal model for MS. This proposal will examine the regulation of the immune system response by epicutaneous (skin) immunization with self-antigen. Epicutaneous immunization is a process whereby, a skin patch soaked in antigen, in this case the CNS antigen myelin oligodendrocyte gylcpprotein (MOG), is applied to the shaved skin of mice prior to inducing EAE with the same antigen. We have recently shown that when we carry out epicutaneous immunization or skin patching with MOG in C57BL/6 mice prior to EAE induction that these mice are protected from developing EAE. Most importantly, when we apply epicutaneous immunization to mice after they develop EAE, mice with mild EAE are protected, but not mice with severe EAE. We observed that the CD4 T cells from mice that are protected from EAE produced high levels of IL-10 and they can transfer protection to na¿ve recipient mice. We also found that the epidermal dendritic cells in the skin that captured antigen from the patch can suppress EAE when they are isolated from the skin after epicutaneous immunization and transferred into na¿ve recipient mice. The goal of this proposal is set out in three specific aims that will determine 1) whether epicutaneous immunization/skin patching with MOG can ameliorate ongoing EAE in mice and reduce or prevent relapses; 2) determine whether tolerance mediated by CD4 T cells in mice epicutaneously immunized with MOG is dependent on IL-10 and 3) determine the role of epidermal dendritic cells in epicutaneous immunization-induced tolerance. These studies will serve to advance our knowledge of autoimmune disease regulation both at the peripheral level and at the CNS level and could be beneficial to MS and other autoimmune diseases.