4.8 Review

Effects of sex steroids on thymic epithelium and thymocyte development

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.975858

Keywords

thymocyte development; thymocyte selection; AIRE; androgens; estrogens; progestins

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Funding

  1. Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health

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Sex steroid hormones have significant effects on the thymus, causing thymic atrophy. Thymic epithelial cells (TEC), which are highly responsive to sex steroids, play a crucial role. Endogenous steroids have remarkable programming effects on the synthesis of T cell receptor (TCR) repertoire through TEC.
Sex steroid hormones have major effects on the thymus. Age-related increases in androgens and estrogens and pregnancy-induced increases in progestins all cause dramatic thymic atrophy. Atrophy can also be induced by treatment with exogenous sex steroids and reversed by ablation of endogenous sex steroids. Although these observations are frequently touted as evidence of steroid lymphotoxicity, they are often driven by steroid signaling in thymic epithelial cells (TEC), which are highly steroid responsive. Here, we outline the effects of sex steroids on the thymus and T cell development. We focus on studies that have examined steroid signaling in vivo, aiming to emphasize the actions of endogenous steroids which, via TEC, have remarkable programming effects on the TCR repertoire. Due to the dramatic effects of steroids on TEC, especially thymic involution, the direct effects of sex steroid signaling in thymocytes are less well understood. We outline studies that could be important in addressing these possibilities, and highlight suggestive findings of sex steroid generation within the thymus itself.

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