| Autor: |
Hummel, J., Zeis, P., Fixemer, J., Konrad, P., Schachtrup, C., Arnold, S., Grün, D., Tanriver, Y. |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Mucosal immunology : official journal of the Society for Mucosal Immunology |
| Popis: |
Natural intraepithelial lymphocytes (IELs) are thymus-derived adaptive immune cells, which are important contributors to intestinal immune homeostasis. Similar to other innate-like T cells, they are induced in the thymus through high-avidity interaction that would otherwise lead to clonal deletion in conventional CD4 and CD8 T cells. By applying single-cell RNA-sequencing (scRNA-seq) on a heterogeneous population of thymic CD4−CD8αβ−TCRαβ+NK1.1− IEL precursors (NK1.1− IELPs), we define a developmental trajectory that can be tracked based on the sequential expression of CD122 and T-bet. Moreover, we identify the Id proteins Id2 and Id3 as a novel regulator of IELP development and show that all NK1.1− IELPs progress through a PD-1 stage that precedes the induction of T-bet. The transition from PD-1 to T-bet is regulated by the transcription factor C-Myc, which has far reaching effects on cell cycle, energy metabolism, and the translational machinery during IELP development. In summary, our results provide a high-resolution molecular framework for thymic IEL development of NK1.1− IELPs and deepen our understanding of this still elusive cell type. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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