Increased estrogen to androgen ratio enhances immunoglobulin levels and impairs B cell function in male mice

Juan Antonio Aguilar-Pimentel*, Yi Li Cho, Raffaele Gerlini, Julia Calzada-Wack, Maria Wimmer, Philipp Mayer-Kuckuk, Thure Adler, Carsten B. Schmidt-Weber, Dirk H. Busch, Helmut Fuchs, Valérie Gailus-Durner, Markus Ollert, Martin Hrabě de Angelis, Claes Ohlsson, Matti Poutanen, Raffaele Teperino, Leena Strauss

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number18334
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020

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