| First Author | Nie J | Year | 2022 |
| Journal | Nat Immunol | Volume | 23 |
| Issue | 4 | Pages | 594-604 |
| PubMed ID | 35354951 | Mgi Jnum | J:323861 |
| Mgi Id | MGI:7264846 | Doi | 10.1038/s41590-022-01161-x |
| Citation | Nie J, et al. (2022) The transcription factor LRF promotes integrin beta7 expression by and gut homing of CD8alphaalpha(+) intraepithelial lymphocyte precursors. Nat Immunol 23(4):594-604 |
| abstractText | While T cell receptor (TCR) alphabeta(+)CD8alpha(+)CD8beta(-) intraepithelial lymphocytes (CD8alphaalpha(+) IELs) differentiate from thymic IEL precursors (IELps) and contribute to gut homeostasis, the transcriptional control of their development remains poorly understood. In the present study we showed that mouse thymocytes deficient for the transcription factor leukemia/lymphoma-related factor (LRF) failed to generate TCRalphabeta(+)CD8alphaalpha(+) IELs and their CD8beta-expressing counterparts, despite giving rise to thymus and spleen CD8alphabeta(+) T cells. LRF-deficient IELps failed to migrate to the intestine and to protect against T cell-induced colitis, and had impaired expression of the gut-homing integrin alpha4beta7. Single-cell RNA-sequencing found that LRF was necessary for the expression of genes characteristic of the most mature IELps, including Itgb7, encoding the beta7 subunit of alpha4beta7. Chromatin immunoprecipitation and gene-regulatory network analyses both defined Itgb7 as an LRF target. Our study identifies LRF as an essential transcriptional regulator of IELp maturation in the thymus and subsequent migration to the intestinal epithelium. |
