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

  • Nat Commun. 2018 May 25;9(1):2067. doi: 10.1038/s41467-018-04408-0.
Anna S Wilhelmson  1  2 ,  Marta Lantero Rodriguez  1 ,  Alexandra Stubelius  3  4 ,  Per Fogelstrand  1 ,  Inger Johansson  1 ,  Matthew B Buechler  5 ,  Steve Lianoglou  5 ,  Varun N Kapoor  5 ,  Maria E Johansson  6 ,  Johan B Fagman  7 ,  Amanda Duhlin  8 ,  Prabhanshu Tripathi  9 ,  Alessandro Camponeschi  10 ,  Bo T Porse  2 ,  Antonius G Rolink  11 ,  Hans Nissbrandt  12 ,  Shannon J Turley  5 ,  Hans Carlsten  3 ,  Inga-Lill Mårtensson  10 ,  Mikael C I Karlsson  8 ,  Åsa Tivesten  13
Affiliations
  • 1. Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45, Gothenburg, Sweden.
  • 2. The Finsen Laboratory, Rigshospitalet; Biotech Research and Innovation Centre (BRIC); Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), Faculty of Health Sciences, University of Copenhagen, Ole Maaløesvej 5, DK-2200, Copenhagen N, Denmark.
  • 3. Center for Bone and Arthritis Research (CBAR), Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, Vita Stråket 11, SE-413 45, Gothenburg, Sweden.
  • 4. Center of Excellence in Nanomedicine and Engineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
  • 5. Department of Cancer Immunology, Genentech, 1 DNA Way, South San Francisco, CA, 94080, USA.
  • 6. Department of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Box 432, SE-405 30, Gothenburg, Sweden.
  • 7. Sahlgrenska Cancer Center, Department of Surgery, Institute of Clinical Sciences, University of Gothenburg, Box 100, SE-405 30, Gothenburg, Sweden.
  • 8. Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77, Stockholm, Sweden.
  • 9. Centre for Human Microbial Ecology, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone Faridabad-Gurgaon Expressway, Faridabad, 121001, Haryana, India.
  • 10. Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Box 480, SE-405 30, Gothenburg, Sweden.
  • 11. Department of Biomedicine, Developmental and Molecular Immunology, University of Basel, Mattenstrasse 28, 4058, Basel, Switzerland.
  • 12. Department of Pharmacology, Institute of Neuroscience and Physiology, University of Gothenburg, Box 431, SE-405 30, Gothenburg, Sweden.
  • 13. Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45, Gothenburg, Sweden. [email protected].
PMID: 29802242 DOI: 10.1038/s41467-018-04408-0
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.

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