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

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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Aguilar-Pimentel JA,Cho YL,Gerlini R,Calzada-Wack J,Wimmer M,Mayer-Kuckuk P,Adler T,Schmidt-Weber CB,Busch DH,Fuchs H,Gailus-Durner V,Ollert M,Hrabě de Angelis M,Ohlsson C,Poutanen M,Teperino R,Strauss L

doi

10.1038/s41598-020-75059-9

subject

Has Abstract

pub_date

2020-10-27 00:00:00

pages

18334

issue

1

issn

2045-2322

pii

10.1038/s41598-020-75059-9

journal_volume

10

pub_type

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