Mesenchymal stem cells ameliorate B-cell-mediated immune responses and increase IL-10-expressing regulatory B cells in an EBI3-dependent manner
Mesenchymal stem cells ameliorate B-cell-mediated immune responses and increase IL-10-expressing regulatory B cells in an EBI3-dependent manner
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DOI：
10.1038/cmi.2016.59
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发表时间：
2017-11-01
影响因子：
24.1
通讯作者：
Ryu, Kyung-Ha
中科院分区：
文献类型：
--
作者：
Cho, Kyung-Ah;Lee, Jun-Kyu;Ryu, Kyung-Ha
效应B细胞通过激活自身反应性T细胞、产生促炎细胞因子和组织异位淋巴组织，是自身免疫性疾病发展的中心贡献者。相反，产生IL-10的调节性B(B-reg)细胞在维持免疫耐受和抑制自身炎症性疾病的过度炎症中起着关键作用。因此，调节产生抗体的效应B细胞和B-reg细胞之间的平衡对于自身免疫性疾病的治疗至关重要。在这项研究中，我们研究了人腭扁桃体来源的间充质干细胞(T-MSCs)在体内和体外对雌激素(E2)诱导的B细胞反应的影响。将T-MSC移植到E2治疗的小鼠体内可以减轻B细胞介导的免疫反应，并增加产生IL-10的B-reg细胞的数量。T-MSCs通过产生EB病毒(EBV)诱导3(EBI3)来调节B细胞群，EBI3是IL-35的两个亚基之一，是众所周知的B-reg细胞的诱导剂。我们在体外通过消耗T-MSCs中的EBI3和在培养系统中加入外源IL-35来证明EBI3(IL-35)的关键作用。综上所述，我们的数据表明，分泌IL-35的MSCs可能成为一种有吸引力的治疗方法，通过扩增B-reg细胞来治疗B细胞介导的自身免疫性疾病。
Effector B cells are central contributors to the development of autoimmune disease by activating autoreactive T cells, producing pro-inflammatory cytokines and organizing ectopic lymphoid tissue. Conversely, IL-10-producing regulatory B (B-reg) cells have pivotal roles in maintaining immunological tolerance and restraining excessive inflammation in autoinflammatory disease. Thus, regulating the equilibrium between antibody-producing effector B cells and B-reg cells is critical for the treatment of autoimmune disease. In this study, we investigated the effect of human palatine tonsil-derived mesenchymal stem cells (T-MSCs) on estradiol (E2)-induced B-cell responses in vivo and in vitro. Transplantation of T-MSC into E2-treated mice alleviated B-cell-mediated immune responses and increased the population of IL-10-producing B-reg cells. T-MSCs regulated the B-cell populations by producing Epstein-Barr virus (EBV)-induced 3 (EBI3), one of the two subunits of IL-35 that is the well-known inducer of B-reg cells. We demonstrate a critical role of EBI3 (IL-35) in vitro by depleting EBI3 in T-MSCs and by adding exogenous IL-35 to the culture system. Taken together, our data suggest that IL-35-secreting MSCs may become an attractive therapeutic to treat B-cell-mediated autoimmune diseases via expanding B-reg cells.