Toll-like receptor driven B cell activation in the induction of systemic autoimmunity.
Toll-like receptor driven B cell activation in the induction of systemic autoimmunity.
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DOI：
10.1016/j.smim.2011.01.016
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发表时间：
2011-04
影响因子：
7.8
通讯作者：
Marshak-Rothstein A
中科院分区：
文献类型：
--
作者：
Green NM;Marshak-Rothstein A
过去十年的研究表明，模式识别受体在自身反应性B细胞的激活中起着关键作用。设法逃避负选择的自反应性B细胞通常对自身抗原表达相对较低的亲和力受体（无知B细胞），并且只能通过将相对较弱的BCR信号与来自其他受体的信号整合来激活。toll样受体（TLR）基因家族的成员，尤其是核酸结合受体tlr7、8和9，似乎在这方面发挥了关键作用，并促进了与DNA或rna相关自身抗原反应的自身抗体的产生。这些自身抗体能够与可溶性或细胞结合的配体形成免疫复合物，这些免疫复合物反过来可以激活第二轮促炎细胞，进一步促进自身免疫性疾病的进程。最近的数据显示，TLR7具有致病作用，而TLR9具有相反的保护作用。针对这些失调的途径提供了一个治疗自身免疫性疾病而不损害整个免疫系统的治疗机会。进一步了解控制这些tlr相关通路的特定受体、细胞亚群和抑制信号的作用，将使未来的治疗方法能够针对自身免疫性疾病的特定类别进行定制。
Studies over the past decade have demonstrated a key role for pattern recognition receptors in the activation of autoreactive B cells. Self reactive B cells that manage to escape negative selection often express relatively low affinity receptors for self antigens (ignorant B cells), and can only be activated by integrating a relatively weak BCR signal with signals from additional receptors. Members of the toll-like receptor (TLR) gene family, and especially the nucleic acid binding receptors TLR 7, 8 and 9, appear to play a key role in this regard and promote the production of autoantibodies reactive with DNA- or RNA-associated autoantigens. These autoantibodies are able to form immune complexes with soluble or cell-bound ligands, and these immune complexes can in turn activate a second round of proinflammatory cells that further contribute to the autoimmune disease process. Recent data have emerged showing a pathogenic role for TLR7, with an opposing, protective role for TLR9. Targeting these disregulated pathways offers a therapeutic opportunity to treat autoimmune diseases without crippling the entire immune system. Further understanding of the role of specific receptors, cell subsets, and inhibitory signals that govern these TLR-associated pathways will enable future therapeutics to be tailored to specific categories of autoimmune disease.
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