Androgens Regulate Bone Marrow B Lymphopoiesis in Male Mice by Targeting Osteoblast-Lineage Cells

Wilhelmson, Anna S.; Stubelius, Alexandra; Börjesson, Anna; Wu, Jianyao; Stern, Anna; Malin, Stephen; Mårtensson, Inga‐Lill; Ohlsson, Claes; Carlsten, Hans; Tivesten, Åsa

doi:10.1210/en.2014-1822

Cited by 18 publications

(18 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Estrogen can also drive CD5 + B cells to produce autoantibodies53. Androgens inhibit bone marrow B lymphopoiesis54 and testosterone reduced the frequency of B220 + cells in lacrimal glands of the SjS s MRL/lpr mouse model55. Our data indicate that IL-17 can influence the development of germinal center and plasma B cells.…”

Section: Discussionmentioning

confidence: 99%

Sexual dimorphic function of IL-17 in salivary gland dysfunction of the C57BL/6.NOD-Aec1Aec2 model of Sjögren’s syndrome

Voigt

Esfandiary

Wanchoo

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Interleukin (IL)-17 is one of the critical inflammatory cytokines that plays a direct role in development of Sjögren’s syndrome (SjS), a systemic autoimmune disease characterized by a progressive chronic attack against the exocrine glands. The expression levels of IL-17 are correlated with a number of essential clinical parameters such as focus score and disease duration in human patients. Significantly immunological differences of Th17 cells were detected at the onset of clinical disease in female SjS mice compared to males. To further define the role of IL-17 in SjS and elucidate its involvement in the sexual dimorphism, we examined the systemic effect of IL-17 by genetically ablating Il-17 in the C57BL/6.NOD-Aec1Aec2, spontaneous SjS murine model. The results indicate that IL-17 is a potent inflammatory molecule in the induction of chemoattractants, cytokines, and glandular apoptosis in males and females. Elimination of IL-17 reduced sialadenitis more drastically in females than males. IL-17 is highly involved in modulating Th2 cytokines and altering autoantibody profiles which has a greater impact on changing plasma cells and germinal center B cell populations in females than males. The result supports a much more important role for IL-17 and demonstrates the sexual dimorphic function of IL-17 in SjS.

show abstract

Section: Discussionmentioning

confidence: 99%

Sexual dimorphic function of IL-17 in salivary gland dysfunction of the C57BL/6.NOD-Aec1Aec2 model of Sjögren’s syndrome

Voigt

Esfandiary

Wanchoo

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…How sex steroids control B cell number is only partially understood. Male mice with germline deletion of the AR exhibit increased B cells in the bone marrow (17,562). Deletion of the AR gene in either osteoblast-lineage cells or in B lymphocytes also increases B cell number in the bone marrow, suggesting that androgens act both directly and indirectly on B cells to suppress their number (17,562).…”

Section: A B and T Lymphocytesmentioning

confidence: 99%

Estrogens and Androgens in Skeletal Physiology and Pathophysiology

Almeida

Laurent

Dubois

et al. 2017

Physiological Reviews

581

502

View full text Add to dashboard Cite

Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution.

show abstract

“…Removal of endogenously produced androgens by castration of male mice induces expansion of both the bone marrow and the splenic B-cell populations, which can be reversed by androgen treatment 20 . The suppressive androgenic effect on B lymphopoiesis has been shown to be mediated via androgen-sensitive stromal cells in the bone marrow 20 , 25 , 26 , 44 .…”

Section: Discussionmentioning

confidence: 99%

“…Castration of male mice also increases thymic and peripheral CD4 + T-cell numbers 21 . Androgens may exert their effects directly via hormone receptors expressed by lymphocytes 22 – 24 , but the effects of testosterone and DHT on B- and T cells may also occur indirectly by androgen targeting of stromal cells and osteoblast-lineage cells in the bone marrow 25 , 26 . In newborn children, umbilical cord blood testosterone and DHT levels are higher in boys compared to girls 27 , 28 .…”

Section: Introductionmentioning

confidence: 99%

Dihydrotestosterone levels at birth associate positively with higher proportions of circulating immature/naïve CD5+ B cells in boys

Lundell

Nordström

Andersson

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Boys present with higher proportions of immature/naïve CD5+ B cells than girls up to 3 years of age. Boys also have higher fractions of regulatory T cells (Tregs) in early infancy, but the mechanisms for these sex-related differences are unknown. In the prospective FARMFLORA follow-up study of 23 boys and 25 girls, we investigated if these immunological differences remained at 8 years of age. We also examined if testosterone or dihydrotestosterone (DHT) levels at birth and at 8 years of age were associated with immune maturation. Immunological variables and androgen levels were examined and measured in blood samples obtained at birth, 3–5 days and at 8 years of age. Boys had higher proportions of CD5+ and immature/transitional CD24hiCD38hi B cells, whereas girls had higher fractions of B cells with a memory phenotype at 8 years of age. School-aged boys also presented with higher frequencies of Tregs, and a greater capacity to produce T-cell-associated cytokines. Among boys, higher cord blood DHT levels were associated with higher proportions of CD5+ B cells in early infancy and at 8 years of life. These results suggest that DHT actions in utero might be involved in the mechanism for delayed peripheral B-cell maturation in boys.

show abstract

Androgens Regulate Bone Marrow B Lymphopoiesis in Male Mice by Targeting Osteoblast-Lineage Cells

Cited by 18 publications

References 43 publications

Sexual dimorphic function of IL-17 in salivary gland dysfunction of the C57BL/6.NOD-Aec1Aec2 model of Sjögren’s syndrome

Sexual dimorphic function of IL-17 in salivary gland dysfunction of the C57BL/6.NOD-Aec1Aec2 model of Sjögren’s syndrome

Estrogens and Androgens in Skeletal Physiology and Pathophysiology

Dihydrotestosterone levels at birth associate positively with higher proportions of circulating immature/naïve CD5+ B cells in boys

Contact Info

Product

Resources

About