title: Androgens regulate bone marrow B lymphopoiesis in male mice by targeting osteoblast-lineage cells.
abstract: 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.
authors: Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., Å.T.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden; Centre for Bone and Arthritis Research (A.Stu., A.E.B., J.W., C.O., H.C.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden; Department of Rheumatology and Inflammation Research (A.Ste., I.-L.M.), University of Gothenburg, 405 30 Gothenburg, Sweden; and Department of Medicine (S.M.), Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors: Anna S
authors: AS
authors: Wilhelmson
authors: Alexandra
authors: A
authors: Stubelius
authors: Anna E
authors: AE
authors: Börjesson
authors: Jianyao
authors: J
authors: Wu
authors: Anna
authors: A
authors: Stern
authors: Stephen
authors: S
authors: Malin
authors: Inga-Lill
authors: IL
authors: Mårtensson
authors: Claes
authors: C
authors: Ohlsson
authors: Hans
authors: H
authors: Carlsten
authors: Åsa
authors: Å
authors: Tivesten
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D001853:Bone Marrow / Q000378:metabolism; D019070:Cell Lineage; D024042:Collagen Type I / Q000097:blood; D038041:Lymphopoiesis / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000097:blood; D010455:Peptides / Q000097:blood; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
chemical_list: D000728:Androgens; D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; D011944:Receptors, Androgen; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin