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Androgens regulate bone marrow B lymphopoiesis in male mice by targeting osteoblast-lineage cells.

Artikel i vetenskaplig tidskrift
Författare Anna S K Wilhelmson
Alexandra Stubelius
Anna E Börjesson
Jianyao Wu
Anna Stern
Stephen Malin
Inga-Lill Mårtensson
Claes Ohlsson
Hans Carlsten
Åsa Tivesten
Publicerad i Endocrinology
Volym 156
Nummer/häfte 4
Sidor 1228-36
ISSN 1945-7170
Publiceringsår 2015
Publicerad vid Wallenberglaboratoriet
Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning
Centre for Bone and Arthritis Research
Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
Sidor 1228-36
Språk en
Länkar dx.doi.org/10.1210/en.2014-1822
https://gup.ub.gu.se/file/175647
Ämneskategorier Klinisk medicin, Endokrinologi

Sammanfattning

Testosterone has profound immune-modulatory actions, which may be important for the sexual dimorphism in immune-related disorders, such as autoimmune diseases. A well-known effect of androgens is inhibition of bone marrow B lymphopoiesis; however, a plausible target cell for this effect has not yet been presented. The aim of this study was to determine the target cell for androgen-mediated regulation of bone marrow B lymphopoiesis in males. We confirm higher number of bone marrow B cells in male mice with global inactivation of the androgen receptor (AR) and these global AR knockout (G-ARKO) mice had increased number of B cell precursors from the pro-B stage. Because osteoblast-lineage cells are known to support B lymphopoiesis at the pro-B stage, we investigated the effect on B lymphopoiesis in osteoblast-lineage cell-specific ARKO (O-ARKO) mice; O-ARKO mice had increased number of B cells in the bone marrow, and the number of B cell precursors was increased from the pro-B stage, demonstrating that O-ARKO mimics the bone marrow B lymphopoiesis pattern of G-ARKO mice. By contrast, O-ARKO mice displayed only minor changes in B cell numbers in the splenic compartment compared with G-ARKO. Further, O-ARKO mice had moderately reduced number of bone trabeculae in the vertebrae, whereas cortical bone was unaffected. In conclusion, androgens exert inhibitory effects on bone marrow B lymphopoiesis in males by targeting the AR in osteoblast-lineage cells. The identification of the likely target cell for androgen-mediated regulation of bone marrow B lymphopoiesis will contribute to elucidation of the mechanisms by which androgens modulate immune-related disorders.

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