Testosterone is an endogenous regulator of BAFF and splenic B cell number
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Testosterone is an endogenous regulator of BAFF and splenic B cell number. / Wilhelmson, Anna S.; Lantero Rodriguez, Marta; Stubelius, Alexandra; Fogelstrand, Per; Johansson, Inger; Buechler, Matthew B.; Lianoglou, Steve; Kapoor, Varun N.; Johansson, Maria E.; Fagman, Johan B.; Duhlin, Amanda; Tripathi, Prabhanshu; Camponeschi, Alessandro; Porse, Bo T.; Rolink, Antonius G.; Nissbrandt, Hans; Turley, Shannon J.; Carlsten, Hans; Mårtensson, Inga-Lill; Karlsson, Mikael C. I.; Tivesten, Åsa.
I: Nature Communications, Bind 9, 2067, 2018, s. 1-13.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
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
Y1 - 2018
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
VL - 9
SP - 1
EP - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 2067
ER -
ID: 199464842