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- Title
Testosterone is an endogenous regulator of BAFF and splenic B cell number.
- Authors
Buechler, Matthew B.; Lantero Rodriguez, Marta; Fogelstrand, Per; Johansson, Inger; Tivesten, Åsa; Wilhelmson, Anna S.; Duhlin, Amanda; Karlsson, Mikael C. I.; Tripathi, Prabhanshu; Camponeschi, Alessandro; Mårtensson, Inga-Lill; Rolink, Antonius G.; Nissbrandt, Hans; Porse, Bo T.; Carlsten, Hans; Stubelius, Alexandra; Lianoglou, Steve; Kapoor, Varun N.; Turley, Shannon J.; Johansson, Maria E.
- Abstract
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.
- Subjects
TESTOSTERONE; HORMONE deficiencies; HORMONE regulation; SPLEEN; TALL-1 (Protein); AUTOIMMUNITY
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-04408-0