Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China; Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Hefei, China; Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, China.
Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China; Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Hefei, China; Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, China.
Biomed Pharmacother. 2019 Jun;114:108796. doi: 10.1016/j.biopha.2019.108796. Epub 2019 Mar 25.
B-cell activating factor from the tumor necrosis factor family (BAFF) has revealed its critical role in B cell proliferation and survival, as well as the pathogenesis of T-cell mediated autoimmune disease. However, the effect and molecular mechanisms of BAFF on T cell physiological function have not been fully elucidated. In this study it was seen that BAFF can promote the vitality of purified T cells, increase the proportion of CD3CD4, CD4CD25, CD4CD154, and CD4CD69 subgroups and reduce the proportion of CD4CD62L subgroups. Negating BAFF activity with Atacicept (TACI-Fc) reverses vitality and activation of T cells. Furthermore, immunofluorescence detection revealed that BAFF promotes the expression of BAFF receptor (BAFF-R) and transmembrane activator and CAML interactor (TACI) in T cells. Flow cytometry displayed that BAFF/BAFF-R activates the PI3K-Akt signaling pathway while the application of PI3K inhibitor (wortmannin) illuminated that BAFF induces T cell vitality and activation through the PI3K-Akt signaling pathway. We conclude that BAFF is involved in not only the physiology of B cells, but also that of T cells. BAFF affects physiological T-cell activation through BAFF-R-mediated activation of the PI3K-Akt signaling pathway which mirrors one of the pathological mechanisms of T cell-mediated autoimmune diseases.
B 细胞激活因子（BAFF）属于肿瘤坏死因子家族，其在 B 细胞增殖和存活以及 T 细胞介导的自身免疫性疾病发病机制中发挥着关键作用。然而，BAFF 对 T 细胞生理功能的影响及其分子机制尚未完全阐明。在本研究中发现，BAFF 可促进纯化 T 细胞的活力，增加 CD3CD4+、CD4CD25+、CD4CD154+和 CD4CD69+亚群的比例，并降低 CD4CD62L+亚群的比例。用 Atacicept（TACI-Fc）拮抗 BAFF 活性可逆转 T 细胞的活力和激活。此外，免疫荧光检测显示，BAFF 可促进 T 细胞中 BAFF 受体（BAFF-R）和跨膜激活剂和钙调神经磷酸酶相互作用因子（TACI）的表达。流式细胞术显示，BAFF/BAFF-R 激活 PI3K-Akt 信号通路，而 PI3K 抑制剂（wortmannin）的应用表明，BAFF 通过 PI3K-Akt 信号通路诱导 T 细胞活力和激活。我们的结论是，BAFF 不仅参与 B 细胞的生理功能，而且还参与 T 细胞的生理功能。BAFF 通过 BAFF-R 介导的 PI3K-Akt 信号通路的激活来影响 T 细胞的生理激活，这反映了 T 细胞介导的自身免疫性疾病的一种病理机制。
