Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45, Gothenburg, Sweden.
The Finsen Laboratory, Rigshospitalet; Biotech Research and Innovation Centre (BRIC); Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), Faculty of Health Sciences, University of Copenhagen, Ole Maaløesvej 5, DK-2200, Copenhagen N, Denmark.
Nat Commun. 2018 May 25;9(1):2067. doi: 10.1038/s41467-018-04408-0.
Testosterone deficiency in men is associated with increased risk for autoimmunity and increased B cell numbers through unknown mechanisms. Here we show that testosterone regulates the cytokine BAFF, an essential survival factor for B cells. Male mice lacking the androgen receptor have increased splenic B cell numbers, serum BAFF levels and splenic Baff mRNA. Testosterone deficiency by castration causes expansion of BAFF-producing fibroblastic reticular cells (FRCs) in spleen, which may be coupled to lower splenic noradrenaline levels in castrated males, as an α-adrenergic agonist decreases splenic FRC number in vitro. Antibody-mediated blockade of the BAFF receptor or treatment with the neurotoxin 6-hydroxydopamine revert the increased splenic B cell numbers induced by castration. Among healthy men, serum BAFF levels are higher in men with low testosterone. Our study uncovers a previously unrecognized regulation of BAFF by testosterone and raises important questions about BAFF in testosterone-mediated protection against autoimmunity.
男性睾丸激素缺乏与自身免疫风险增加和 B 细胞数量增加有关，但具体机制尚不清楚。在这里，我们发现睾丸激素可以调节细胞因子 BAFF，这是 B 细胞生存的必需因子。缺乏雄激素受体的雄性小鼠的脾脏 B 细胞数量、血清 BAFF 水平和脾脏 Baff mRNA 均增加。去势导致雄性小鼠的睾丸激素缺乏会引起脾脏中产生 BAFF 的纤维母细胞网状细胞（FRC）扩张，这可能与去势雄性动物的脾脏去甲肾上腺素水平降低有关，因为 α-肾上腺素能激动剂可减少体外脾脏 FRC 的数量。BAFF 受体的抗体阻断或神经毒素 6-羟多巴胺的治疗可逆转去势引起的脾脏 B 细胞数量增加。在健康男性中，睾丸激素水平低的男性血清 BAFF 水平更高。我们的研究揭示了睾丸激素对 BAFF 的一种以前未被认识的调节作用，并提出了关于 BAFF 在睾丸激素介导的自身免疫保护中的重要问题。
