BAFF Induces Tertiary Lymphoid Structures and Positions T Cells within the Glomeruli during Lupus Nephritis.
BAFF Induces Tertiary Lymphoid Structures and Positions T Cells within the Glomeruli during Lupus Nephritis.
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DOI：
10.4049/jimmunol.1600281
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发表时间：
2017-04-01
期刊：
影响因子：
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通讯作者：
Vilen BJ
中科院分区：
文献类型：
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作者：
Kang S;Fedoriw Y;Brenneman EK;Truong YK;Kikly K;Vilen BJ
组织特异性免疫应答在自身免疫性疾病的病理学中起着重要作用。在系统性红斑狼疮（SLE）中，IgG免疫复合物的沉积和补体在肾脏中的活化长期以来被认为是促进炎症和狼疮性肾炎的原因。然而，在非淋巴三级器官中定位细胞并维持组织特异性免疫应答的事件仍然不确定。在这份手稿中，我们表明，B细胞活化因子的TNF家族（BAFF）促进事件导致狼疮肾炎。使用诱导型SLE模型，我们发现将抗核小体IgG被动转移到AID −/− MRL/lpr小鼠中可提高自身抗体水平，并通过诱导肾脏中BAFF的产生和肾脏三级淋巴样结构（TLS）的形成促进狼疮性肾炎。减少体内BAFF可防止TLS和狼疮性肾炎的形成;然而，它并不能减少免疫细胞浸润或IgG和补体在肾脏中的沉积。从机制上讲，降低BAFF水平也减少了位于肾小球内的T细胞数量，并减少了炎症。因此，BAFF通过诱导肾TLSs和调节T细胞在肾小球内的位置在狼疮肾炎中起着以前未被认识到的作用。
Tissue-specific immune responses play an important role in the pathology of autoimmune diseases. In systemic lupus erythematosus (SLE), deposits of IgG-immune complexes and the activation of complement in the kidney have long been thought to promote inflammation and lupus nephritis. However, the events that localize cells in non-lymphoid tertiary organs and sustain tissue-specific immune responses remain undefined. In this manuscript, we show that B cell activating factor of the TNF family (BAFF) promotes events leading to lupus nephritis. Using an inducible model of SLE, we found that passive transfer of anti-nucleosome IgG into AID−/−MRL/lpr mice elevated autoantibody levels and promoted lupus nephritis by inducing BAFF production in the kidneys, and the formation of renal tertiary lymphoid structures (TLSs). Reducing BAFF in vivo prevented the formation of TLSs and lupus nephritis; however, it did not reduce immune cell infiltrates, or the deposits of IgG and complement in the kidney. Mechanistically, lowering BAFF levels also diminished the number of T cells positioned inside the glomeruli and reduced inflammation. Thus, BAFF plays a previously unappreciated role in lupus nephritis by inducing renal TLSs and regulating the position of T cells within the glomeruli.