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Testosterone is an endogenous regulator of BAFF and splenic B cell number

Journal article
Authors Anna S K Wilhelmson
Marta Lantero Rodriguez
Alexandra Stubelius
Per Fogelstrand
Inger Johansson
M. B. Buechler
S. Lianoglou
V. N. Kapoor
Maria E Johansson
Johan Bourghardt Fagman
A. Duhlin
P. Tripathi
Alessandro Camponeschi
B. T. Porse
A. G. Rolink
Hans Nissbrandt
S. J. Turley
Hans Carlsten
Inga-Lill Mårtensson
M. C. I. Karlsson
Åsa Tivesten
Published in Nature Communications
Volume 9
Issue 1
ISSN 2041-1723
Publication year 2018
Published at Wallenberg Laboratory
Institute of Clinical Sciences, Department of Surgery
Institute of Neuroscience and Physiology, Department of Physiology
Sahlgrenska Cancer Center
Institute of Medicine, Department of Rheumatology and Inflammation Research
Centre for Bone and Arthritis Research
Institute of Neuroscience and Physiology, Department of Pharmacology
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Language en
Links dx.doi.org/10.1038/s41467-018-04408...
Keywords levels inversely correlate, androgen receptor, immunological features, klinefelters-syndrome, tyrosine-hydroxylase, systemic-lupus, murine, lupus, sex-hormone, male-mice, homeostasis
Subject categories Rheumatology and Autoimmunity

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 fibro-blastic reticular cells (FRCs) in spleen, which may be coupled to lower splenic noradrenaline levels in castrated males, as an alpha-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.

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