Participation of B-cell-activating factor receptors in the pathogenesis of immune thrombocytopenia
Participation of B-cell-activating factor receptors in the pathogenesis of immune thrombocytopenia
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B细胞激活因子受体参与免疫性血小板减少症的发病机制
DOI：
10.1111/jth.13246
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发表时间：
2016-03-01
影响因子：
10.4
通讯作者：
Shi, Y.
中科院分区：
文献类型：
--
作者：
Min, Y. -N.;Wang, C. -Y.;Shi, Y.
功能失调的B细胞激活因子（BAFF）系统与许多自身免疫性疾病有关。在体外共培养系统中研究BAFF/BAFF受体的调节功能。BAFF通过不同的受体在免疫性血小板减少症中的不同调节作用进行了研究。自身反应性淋巴细胞上BAFF受体的上调导致其对BAFF.Summary背景的超敏反应，免疫性血小板减少症（ITP）的发病机制仍然是个谜。B细胞活化因子（BAFF）及其受体（BAFF受体[BAFF-R]，跨膜激活剂和钙调节剂和亲环蛋白配体相互作用剂[TACI]，和B细胞成熟抗原）在淋巴细胞的综合稳态调节中发挥核心作用。目的探讨BAFF受体在调节ITP淋巴细胞生物活性中的病理作用。方法通过刺激建立体外培养体系，CD 14（-）外周淋巴细胞与血小板预载树突状细胞在重组人BAFF（rhBAFF; 20 ng mL（-1））的存在下。结果BAFF-R不仅能延长ITP患者和健康对照组B细胞的存活时间，还能显著促进ITP患者CD 8（+）T细胞的存活和B细胞的增殖。TACI作为一种正性调节剂，不仅能促进ITP患者CD 4+和CD 8 + T细胞的增殖，而且能显著增加IL-4的分泌，而对照组则无此作用。除了揭示BAFF受体的病理作用外，这些结果还表明，ITP患者的淋巴细胞与健康对照组相比，在类似的rhBAFF刺激下暴露时，具有增强的抗凋亡或增殖能力。结论ITP患者外周血活化的自身反应性B细胞和CD 4（+）T细胞中BAFF-R和TACI的表达均高于正常对照组。在ITP患者中，它们的异常表达可能导致活化的自身反应性淋巴细胞对rhBAFF的高反应性，因此在ITP的发病机制中具有重要意义。
Dysfunctional B-cell-activating factor (BAFF) system is related to many autoimmune diseases. The regulatory functions of BAFF/BAFF receptors were investigated in an in vitro coculture system. Different regulatory roles of BAFF were investigated via different receptors in immune thrombocytopenia. The upregulated BAFF receptors on autoreactive lymphocytes lead to their hypersensitivity to BAFF.Summary Background The pathogenesis of immune thrombocytopenia (ITP) remains enigmatic. B-cell-activating factor (BAFF) and its receptors (BAFF receptor [BAFF-R], transmembrane activator and calcium modulator and cyclophilin ligand interactor [TACI], and B-cell maturation antigen) play central roles in the integrated homeostatic regulation of lymphocytes.Objectives To investigate the pathologic roles of BAFF receptors in regulating the bioactivities of lymphocytes in ITP.Methods An in vitro culture system was established by stimulating CD14(-) peripheral lymphocytes with platelet-preloaded dendritic cells in the presence of recombinant human BAFF (rhBAFF; 20 ng mL(-1)). The functions of BAFF receptors were specifically blocked with blocking antibodies.Results BAFF-R, besides prolonging the survival of B cells in both patients and healthy controls, prominently promoted the survival of CD8(+) T cells and the proliferation of B cells in patients with ITP. TACI, as a positive regulator, not only promoted the proliferation of CD4(+) and CD8(+) T cells, but also significantly enhanced the secretion of interleukin-4 in patients with ITP, but not in controls. Besides revealing the pathologic roles of BAFF receptors, these results also indicate that lymphocytes of patients with ITP have enhanced antiapoptotic or proliferative capacity as compared with those from healthy controls when exposed under similar stimulation of rhBAFF. Further study demonstrated that activated autoreactive B cells and CD4(+) T cells from patients with ITP showed significantly higher expression of BAFF-R or TACI than those from healthy controls.Conclusions Both BAFF-R and TACI are pathogenic participants in ITP. Their dysregulated expression in patients with ITP may lead to hyperreactivity of activated autoreactive lymphocytes in response to rhBAFF, and thus is highly significant in the pathogenesis of ITP.