Wilhelmson AS, Stubelius A, Borjesson AE, Wu J, Stern A, et al. Androgens Regulate Bone Marrow B Lymphopoiesis in Male Mice by Targeting Osteoblast-Lineage Cells. Endocrinology. http://press.endocrine.org/doi/abs/10.1210/en.2014-1822
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 G-ARKO mice had increased number of B cell precursors from the pro-B stage.
Since 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 to G-ARKO. Further, O-ARKO mice had moderately reduced number of bone trabeculae in the vertebrae while 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.
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 G-ARKO mice had increased number of B cell precursors from the pro-B stage.
Since 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 to G-ARKO. Further, O-ARKO mice had moderately reduced number of bone trabeculae in the vertebrae while 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.
