TY - JOUR
T1 - Increased estrogen to androgen ratio enhances immunoglobulin levels and impairs B cell function in male mice
AU - Aguilar-Pimentel, Juan Antonio
AU - Cho, Yi Li
AU - Gerlini, Raffaele
AU - Calzada-Wack, Julia
AU - Wimmer, Maria
AU - Mayer-Kuckuk, Philipp
AU - Adler, Thure
AU - Schmidt-Weber, Carsten B.
AU - Busch, Dirk H.
AU - Fuchs, Helmut
AU - Gailus-Durner, Valérie
AU - Ollert, Markus
AU - Hrabě de Angelis, Martin
AU - Ohlsson, Claes
AU - Poutanen, Matti
AU - Teperino, Raffaele
AU - Strauss, Leena
N1 - Funding Information:
The Authors thanks Julia Wittmann, Florian Schleicher and Dr. Stefanie Leuchtenberger (GMC) and Heidi Liljenbäck, Katri Hovirinta, Nina Messner, Heli Niittymäki and Jonna Palmu (TCDM) for technical support and advice. This study was supported by Jalmari and Rauha Ahokas Foundation, Foundation of Allergy Research (Finnish), Academy of Finland, Sigrid Juselius Foundation and by the German Federal Ministry of Education and Research (Infrafrontier Grant 01KX1012), the German Center for Diabetes Research (DZD) and the Helmholtz Alliance ‘Aging and Metabolic Programming, AMPro’.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Sex steroids, such as estrogens and androgens, are important regulators of the humoral immune response. Studies in female mice have demonstrated that alteration of circulating estrogen concentration regulates antibody-mediated immunity. As males have normally little endogenous estrogen, we hypothesized that in males high estrogens and low androgens affect the immune system and enhance the allergic inflammatory response. Here, we studied transgenic male mice expressing human aromatase (AROM+). These animals have a high circulating estrogen to androgen ratio (E/A), causing female traits such as gynecomastia. We found that AROM+ male mice had significantly higher plasma immunoglobulin levels, particularly IgE. Flow cytometry analyses of splenocytes revealed changes in mature/immature B cell ratio together with a transcriptional upregulation of the Igh locus. Furthermore, higher proliferation rate and increased IgE synthesis after IgE class-switching was found. Subsequently, we utilized an ovalbumin airway challenge model to test the allergic response in AROM+ male mice. In line with above observations, an increase in IgE levels was measured, albeit no impact on immune cell infiltration into the lungs was detected. Together, our findings suggest that high circulating E/A in males significantly alters B cell function without any significant enhancement in allergic inflammation.
AB - Sex steroids, such as estrogens and androgens, are important regulators of the humoral immune response. Studies in female mice have demonstrated that alteration of circulating estrogen concentration regulates antibody-mediated immunity. As males have normally little endogenous estrogen, we hypothesized that in males high estrogens and low androgens affect the immune system and enhance the allergic inflammatory response. Here, we studied transgenic male mice expressing human aromatase (AROM+). These animals have a high circulating estrogen to androgen ratio (E/A), causing female traits such as gynecomastia. We found that AROM+ male mice had significantly higher plasma immunoglobulin levels, particularly IgE. Flow cytometry analyses of splenocytes revealed changes in mature/immature B cell ratio together with a transcriptional upregulation of the Igh locus. Furthermore, higher proliferation rate and increased IgE synthesis after IgE class-switching was found. Subsequently, we utilized an ovalbumin airway challenge model to test the allergic response in AROM+ male mice. In line with above observations, an increase in IgE levels was measured, albeit no impact on immune cell infiltration into the lungs was detected. Together, our findings suggest that high circulating E/A in males significantly alters B cell function without any significant enhancement in allergic inflammation.
UR - http://www.scopus.com/inward/record.url?scp=85094163684&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/33110090
U2 - 10.1038/s41598-020-75059-9
DO - 10.1038/s41598-020-75059-9
M3 - Article
C2 - 33110090
AN - SCOPUS:85094163684
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 18334
ER -