| First Author | Ono K | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 5152 |
| PubMed ID | 37620389 | Mgi Jnum | J:357426 |
| Mgi Id | MGI:7521389 | Doi | 10.1038/s41467-023-40950-2 |
| Citation | Ono K, et al. (2023) Downregulation of chemokine receptor 9 facilitates CD4(+)CD8alphaalpha(+) intraepithelial lymphocyte development. Nat Commun 14(1):5152 |
| abstractText | Intestinal intraepithelial lymphocytes (IELs) reside in the gut epithelial layer, where they help in maintaining intestinal homeostasis. Peripheral CD4(+) T cells can develop into CD4(+)CD8alphaalpha(+) IELs upon arrival at the gut epithelium via the lamina propria (LP). Although this specific differentiation of T cells is well established, the mechanisms preventing it from occurring in the LP remain unclear. Here, we show that chemokine receptor 9 (CCR9) expression is low in epithelial CD4(+)CD8alphaalpha(+) IELs, but CCR9 deficiency results in CD4(+)CD8alphaalpha(+) over-differentiation in both the epithelium and the LP. Single-cell RNA sequencing shows an enriched precursor cell cluster for CD4(+)CD8alphaalpha(+) IELs in Ccr9(-/-) mice. CD4(+) T cells isolated from the epithelium of Ccr9(-/-) mice also display increased expression of Cbfbeta2, and the genomic occupancy modification of Cbfbeta2 expression reveals its important function in CD4(+)CD8alphaalpha(+) differentiation. These results implicate a link between CCR9 downregulation and Cbfb2 splicing upregulation to enhance CD4(+)CD8alphaalpha(+) IEL differentiation. |
