Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China;
J Immunol. 2014 May 1;192(9):4192-201. doi: 10.4049/jimmunol.1302132. Epub 2014 Mar 26.
Clinical trials have shown that BAFF inhibitors do not reduce memory B cell levels but can reduce the number of mature B cells. It remains uncertain whether BAFF affects memory-maintaining cytokines such as IL-15. We found that BAFF suppressed IL-15 expression in B cells from lupus-like or experimental allergic encephalomyelitis mice. When BAFF was blocked with atacicept-IgG, IL-15 expression was upregulated in lupus-like or experimental allergic encephalomyelitis mice. Finally, we showed that BAFF suppressed IL-15 expression in transitional 2 B cells by reducing Foxo1 expression and inducing Foxo1 phosphorylation. This study suggests that BAFF suppresses IL-15 expression in autoimmune diseases, and this opens up the possible opportunity for the clinical application of BAFF- and IL-15-specific therapeutic agents.
临床试验表明，BAFF 抑制剂不会降低记忆 B 细胞水平，但可以减少成熟 B 细胞的数量。目前尚不确定 BAFF 是否会影响维持记忆的细胞因子，如 IL-15。我们发现 BAFF 抑制狼疮样或实验性过敏性脑脊髓炎小鼠 B 细胞中 IL-15 的表达。当用 atacicept-IgG 阻断 BAFF 时，狼疮样或实验性过敏性脑脊髓炎小鼠的 IL-15 表达上调。最后，我们表明 BAFF 通过降低 Foxo1 表达和诱导 Foxo1 磷酸化来抑制过渡性 2B 细胞中的 IL-15 表达。这项研究表明，BAFF 抑制自身免疫性疾病中的 IL-15 表达，这为 BAFF 和 IL-15 特异性治疗剂的临床应用开辟了可能的机会。
