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Ehf and Fezf2 regulate late medullary thymic epithelial cell and thymic tuft cell development
Thymic epithelial cells are indispensable for T cell maturation and selection and the induction of central immune tolerance. The self-peptide repertoire expressed by medullary thymic epithelial cells is in part regulated by the transcriptional regulator Aire (Autoimmune regulator) and the transcr...
Պահպանված է:
| Հիմնական հեղինակներ: | , , , , , , , , , , |
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| Ձևաչափ: | Հոդված |
| Լեզու: | անգլերեն |
| Հրապարակվել է: |
Philipps-Universität Marburg
2024
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| Խորագրեր: | |
| Առցանց հասանելիություն: | PDF ամբողջական տեքստ |
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| Ամփոփում: | Thymic epithelial cells are indispensable for T cell maturation and selection and
the induction of central immune tolerance. The self-peptide repertoire
expressed by medullary thymic epithelial cells is in part regulated by the
transcriptional regulator Aire (Autoimmune regulator) and the transcription
factor Fezf2. Due to the high complexity of mTEC maturation stages (i.e., post-
Aire, Krt10+ mTECs, and Dclk1+ Tuft mTECs) and the heterogeneity in their gene
expression profiles (i.e., mosaic expression patterns), it has been challenging to
identify the additional factors complementing the transcriptional regulation. We
aimed to identify the transcriptional regulators involved in the regulation of
mTEC development and self-peptide expression in an unbiased and genomewide
manner. We used ATAC footprinting analysis as an indirect approach to
identify transcription factors involved in the gene expression regulation in
mTECs, which we validated by ChIP sequencing. This study identifies Fezf2 as
a regulator of the recently described thymic Tuft cells (i.e., Tuft mTECs).
Furthermore, we identify that transcriptional regulators of the ELF, ESE, ERF,
and PEA3 subfamily of the ETS transcription factor family and members of the
Krüppel-like family of transcription factors play a role in the transcriptional
regulation of genes involved in late mTEC development and promiscuous
gene expression. |
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| Նյութի նկարագրություն: | Gefördert durch den Open-Access-Publikationsfonds der UB Marburg. |
| DOI: | 10.3389/fimmu.2023.1277365 |