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Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance

GSE243180 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2024/03/08 Platform GPL19057Platform GPL30172Platform GPL21626
Summary
Medullary thymic epithelial cells (mTECs) are essential for the establishment of self-tolerance in T cells. Promiscuous gene expression by a subpopulation of mTECs regulated by nuclear protein Aire contributes to the display of self-genomic products to newly generated T cells. Recent reports have highlighted additional self-antigen-displaying mTEC subpopulations; namely, Fezf2-expressing mTECs and a mosaic of self-mimetic mTECs including thymic tuft cells. In addition, a functionally different subset of mTECs produces chemokine CCL21 that attracts developing thymocytes to the medullary region. Here we report that CCL21+ mTECs and Aire+ mTECs non-redundantly cooperate to direct self-tolerance to prevent autoimmune pathology by optimizing the deletion of self-reactive T cells and the generation of regulatory T cells. We also detected a cooperation for self-tolerance between Aire and Fezf2, which unexpectedly regulates thymic tuft cells. Our results indicate an indispensable interplay among functionally diverse mTECs for the establishment of central self-tolerance.
Published in
Developmental conversion of thymocyte-attracting cells into self-antigen-displaying cells in embryonic thymus medulla epithelium
Ohigashi I, White AJ, Yang MT et al. · eLife 2024 · PMID 38466627 · doi:10.7554/eLife.92552
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Also filed as BioProject PRJNA1016559 and SRA study SRP460372. Searching any of these in the dataset finder brings you back here.

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