Testosterone is an endogenous regulator of BAFF and splenic B cell number
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- Testosterone is an endogenous regulator of BAFF and splenic B cell number
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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.
Original language | English |
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Article number | 2067 |
Journal | Nature Communications |
Volume | 9 |
Pages (from-to) | 1-13 |
Number of pages | 13 |
ISSN | 2041-1723 |
DOIs | |
Publication status | Published - 2018 |
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