Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance.
Cell Rep
; 43(4): 114072, 2024 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-38581680
ABSTRACT
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 the 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, which 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 detect cooperation for self-tolerance between Aire and Fezf2, the latter of which unexpectedly regulates thymic tuft cells. Our results indicate an indispensable interplay among functionally diverse mTECs for the establishment of central self-tolerance.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Timo
/
Fatores de Transcrição
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Células Epiteliais
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Tolerância Central
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Proteína AIRE
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Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article