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

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

doi:10.1038/s41467-018-04408-0

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

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

Department of Clinical Medicine

22 Citations (Scopus)

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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.

Original language	English
Article number	2067
Journal	Nature Communications
Volume	9
Pages (from-to)	1-13
Number of pages	13
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-018-04408-0
Publication status	Published - 1 Dec 2018

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Testosterone is an endogenous regulator of BAFF and splenic B cell numberFinal published version, 3.48 MBLicence: CC BY

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Wilhelmson, A. S., Lantero Rodriguez, M., Stubelius, A., Fogelstrand, P., Johansson, I., Buechler, M. B., Lianoglou, S., Kapoor, V. N., Johansson, M. E., Fagman, J. B., Duhlin, A., Tripathi, P., Camponeschi, A., Porse, B. T., Rolink, A. G., Nissbrandt, H., Turley, S. J., Carlsten, H., Mårtensson, I.-L., ... Tivesten, Å. (2018). Testosterone is an endogenous regulator of BAFF and splenic B cell number. Nature Communications, 9, 1-13. Article 2067. https://doi.org/10.1038/s41467-018-04408-0

Wilhelmson, AS, Lantero Rodriguez, M, Stubelius, A, Fogelstrand, P, Johansson, I, Buechler, MB, Lianoglou, S, Kapoor, VN, Johansson, ME, Fagman, JB, Duhlin, A, Tripathi, P, Camponeschi, A, Porse, BT, Rolink, AG, Nissbrandt, H, Turley, SJ, Carlsten, H, Mårtensson, I-L, Karlsson, MCI & Tivesten, Å 2018, 'Testosterone is an endogenous regulator of BAFF and splenic B cell number', Nature Communications, vol. 9, 2067, pp. 1-13. https://doi.org/10.1038/s41467-018-04408-0

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title = "Testosterone is an endogenous regulator of BAFF and splenic B cell number",

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.",

author = "Wilhelmson, {Anna S.} and {Lantero Rodriguez}, Marta and Alexandra Stubelius and Per Fogelstrand and Inger Johansson and Buechler, {Matthew B.} and Steve Lianoglou and Kapoor, {Varun N.} and Johansson, {Maria E.} and Fagman, {Johan B.} and Amanda Duhlin and Prabhanshu Tripathi and Alessandro Camponeschi and Porse, {Bo T.} and Rolink, {Antonius G.} and Hans Nissbrandt and Turley, {Shannon J.} and Hans Carlsten and Inga-Lill M{\aa}rtensson and Karlsson, {Mikael C. I.} and {\AA}sa Tivesten",

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doi = "10.1038/s41467-018-04408-0",

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T1 - Testosterone is an endogenous regulator of BAFF and splenic B cell number

AU - Wilhelmson, Anna S.

AU - Lantero Rodriguez, Marta

AU - Stubelius, Alexandra

AU - Fogelstrand, Per

AU - Johansson, Inger

AU - Buechler, Matthew B.

AU - Lianoglou, Steve

AU - Kapoor, Varun N.

AU - Johansson, Maria E.

AU - Fagman, Johan B.

AU - Duhlin, Amanda

AU - Tripathi, Prabhanshu

AU - Camponeschi, Alessandro

AU - Porse, Bo T.

AU - Rolink, Antonius G.

AU - Nissbrandt, Hans

AU - Turley, Shannon J.

AU - Carlsten, Hans

AU - Mårtensson, Inga-Lill

AU - Karlsson, Mikael C. I.

AU - Tivesten, Åsa

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-018-04408-0

DO - 10.1038/s41467-018-04408-0

M3 - Journal article

C2 - 29802242

SN - 2041-1723

VL - 9

SP - 1

EP - 13

JO - Nature Communications

JF - Nature Communications

M1 - 2067

ER -

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

Abstract

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