Aire Drives Steroid Hormone Biosynthesis by Medullary Thymic Epithelial Cells
نویسندگان
چکیده
Abstract Thymocytes progress toward mature T cells through a series of antigen-specific selection steps facilitated by thymic epithelial (TECs) in the cortex, site positive selection, and medulla, negative selection. TECs produce glucocorticoids (GCs), which enhance increase fitness cell repertoire, but TEC subpopultion does this, how it is regulated, unknown. We generated reporter mouse that expresses fusion protein containing Cyp11b1, enzyme mediates last step de novoGC production, fluorescent tag mScarlet knocked into endogenous Cyp11b1locus. found Cyp11b1 exclusively expressed medullary (mTECs), consistent with notion GC antagonize This seemingly at odds fact mTECs facilitate via transcription factor Aire, drives promiscuous expression tissue-restricted antigens (TRAs) vital for establishing central immune tolerance. primarily Aire+ post-Aire absent Aire-deficient mice. Transcriptomic analysis showed most genes biosynthetic pathway are an Aire-dependent manor. Moreover, we their actual steroid product was produced WT not thymi. propose addition to its well-established role inducing TRAs promote Aire has obverse function production together expand TCR repertoire.
منابع مشابه
Post-Aire Maturation of Thymic Medullary Epithelial Cells Involves Selective Expression of Keratinocyte-Specific Autoantigens
The autoimmune regulator (Aire)-directed ectopic expression of tissue-specific antigens (TSAs) by mature medullary thymic epithelial cells (mTECs) has been viewed as an essential mechanism in the induction of central tolerance. Recent data suggest that the survival of mTECs extends beyond the Aire+ cell population to form the post-Aire mTEC population and Hassall's corpuscles (HCs). The nature ...
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.219.12