Journal Article

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

Lantero Rodriguez, Marta, Johansson, Inger, Mårtensson, Inga-Lill, Stubelius, Alexandra, Fagman, Johan B., Duhlin, Amanda, Wilhelmson, Anna S., Camponeschi, Alessandro, Johansson, Maria E., Porse, Bo T., Turley, Shannon J., Rolink, Antonius G., Karlsson, Mikael C. I., Carlsten, Hans, Tripathi, Prabhanshu, Fogelstrand, Per, Buechler, Matthew B., Lianoglou, Steve, Kapoor, Varun N., Tivesten, Åsa, Nissbrandt, Hans

2018

Overview

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. Testosterone deficiency is associated with autoimmunity and increased B cell numbers, but the underlying mechanism is unclear. Here the authors show that testosterone may modulate the production of B cell survival factor BAFF by fibroblastic reticular cells via regulation of splenic neurotransmitter levels.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 6-Hydroxydopamine / 631/250/1619/40/1907 / 631/250/24/1313 / 631/250/371 / 64/110 / 692/163 / Adrenergic alpha-Agonists - pharmacology / androgen receptor / Androgen receptors / Animals / Autoimmune Diseases - immunology / Autoimmune Diseases - metabolism / Autoimmunitet och inflammation / Autoimmunity / Autoimmunity and Inflammation / B-Cell Activating Factor - blood / B-Cell Activating Factor - immunology / B-Cell Activating Factor - metabolism / B-Cell Activation Factor Receptor - antagonists & inhibitors / B-Cell Activation Factor Receptor - metabolism / B-Lymphocytes - drug effects / B-Lymphocytes - immunology / B-Lymphocytes - metabolism / BLyS protein / Castration / Cell number / homeostasis / Humanities and Social Sciences / Humans / immunological features / klinefelters-syndrome / levels inversely correlate / lupus / Lymphocyte receptors / Lymphocytes B / Male / male-mice / Men / Mice / Mice, Knockout / Models, Animal / mRNA / multidisciplinary / murine / Neurotoxins / Noradrenaline / Norepinephrine / Norepinephrine - metabolism / Oxidopamine - pharmacology / Receptors, Androgen - genetics / Receptors, Androgen - metabolism / Rodents / Science / Science (multidisciplinary) / sex-hormone / Spleen / Spleen - cytology / Spleen - drug effects / Spleen - immunology / Survival factor / systemic-lupus / Testosterone / Testosterone - blood / Testosterone - deficiency / Testosterone - immunology / Testosterone - metabolism / tyrosine-hydroxylase