TLR-activated B cells suppress T cell-mediated autoimmunity
TLR-activated B cells suppress T cell-mediated autoimmunity
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DOI：
10.4049/jimmunol.180.7.4763
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发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Fillatreau, Simon
中科院分区：
文献类型：
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作者：
Lampropoulou, Vicky;Hoehlig, Kai;Fillatreau, Simon
TLR检测微生物感染，并控制免疫反应的激活。树突状细胞、巨噬细胞和B淋巴细胞表达TLR和TLR信号传导衔接蛋白MyD88。TLR激活的B细胞对T细胞介导的炎症的影响尚不清楚。在这项研究中，我们使用了MyD 88或不同TLR中携带B细胞限制性缺陷的小鼠，以检查TLR激活的B细胞对T细胞介导的自身免疫性疾病，实验性自身免疫性脑脊髓炎（EAE）的影响。我们证明了B细胞中的TLR信号转导抑制炎性T细胞应答（Th1和Th17），并刺激EAE的恢复。在B细胞上仅需要某些TLR用于EAE的消退，并且这些TLR对于疾病的起始是不可接受的，这表明一类TLR激动剂优先触发B细胞中的抑制功能，从而限制自身免疫性疾病。控制B细胞调节功能的TLR激动剂由佐剂中存在的结核分枝杆菌组分提供。因此，B细胞中的MyD88信号传导拮抗其它细胞中的MyD88信号传导，其驱动Th17细胞的分化并且是诱导EAE所需的。总之，我们的数据表明，B细胞通过TLR将微生物产物的识别与T细胞介导的自身免疫性疾病的抑制联系起来。
TLR sense microbial infections, and control activation of immune responses. Dendritic cells, macrophages, and B lymphocytes express TLR and the TLR-signaling adaptor protein MyD88. The impact of TLR-activated B cells on T cell-mediated inflammation is unknown. In this study, we have used mice carrying B cell-restricted deficiencies in MyD88 or in distinct TLR to examine the impact of TLR-activated B cells on a T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis (EAE). We demonstrate that TLR-signaling in B cells suppresses inflammatory T cell responses (both Th1 and Th17), and stimulates recovery from EAE. Only certain TLR are required on B cells for resolution of EAE, and these are dispensable for disease initiation, indicating that a category of TLR agonists preferentially triggers a suppressive function in B cells and thereby limits autoimmune disease. The TLR agonists controlling the regulatory function of B cells are provided by components of Mycobacterium tuberculosis present in the adjuvant. Thus, MyD88 signaling in B cells antagonizes MyD88 signaling in other cells, which drives differentiation of Th17 cells and is required for induction of EAE. Altogether, our data indicate that B cells link recognition of microbial products via TLR to suppression of a T cell-mediated autoimmune disease.