Testosterone is an endogenous regulator of BAFF and splenic B cell number
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Testosterone is an endogenous regulator of BAFF and splenic B cell number
Forlagets udgivne version, 3,48 MB, PDF-dokument
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.
Originalsprog | Engelsk |
---|---|
Artikelnummer | 2067 |
Tidsskrift | Nature Communications |
Vol/bind | 9 |
Sider (fra-til) | 1-13 |
Antal sider | 13 |
ISSN | 2041-1723 |
DOI | |
Status | Udgivet - 2018 |
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
ID: 199464842