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- Title
Downregulation of chemokine receptor 9 facilitates CD4<sup>+</sup>CD8αα<sup>+</sup> intraepithelial lymphocyte development.
- Authors
Ono, Keiko; Sujino, Tomohisa; Miyamoto, Kentaro; Harada, Yosuke; Kojo, Satoshi; Yoshimatsu, Yusuke; Tanemoto, Shun; Koda, Yuzo; Zheng, Jiawen; Sayama, Kazutoshi; Koide, Tsuyoshi; Teratani, Toshiaki; Mikami, Yohei; Takabayashi, Kaoru; Nakamoto, Nobuhiro; Hosoe, Naoki; London, Mariya; Ogata, Haruhiko; Mucida, Daniel; Taniuchi, Ichiro
- Abstract
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+CD8αα+ 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+CD8αα+ IELs, but CCR9 deficiency results in CD4+CD8αα+ over-differentiation in both the epithelium and the LP. Single-cell RNA sequencing shows an enriched precursor cell cluster for CD4+CD8αα+ IELs in Ccr9−/− mice. CD4+ T cells isolated from the epithelium of Ccr9−/− mice also display increased expression of Cbfβ2, and the genomic occupancy modification of Cbfβ2 expression reveals its important function in CD4+CD8αα+ differentiation. These results implicate a link between CCR9 downregulation and Cbfb2 splicing upregulation to enhance CD4+CD8αα+ IEL differentiation. Peripheral CD4+ T cells can develop into Intestinal intraepithelial lymphocytes (IEL) in the lamina propria. Here the authors characterise how IEL generation from CD4+ T cells is regulated and show using scRNA sequencing that Ccr9 is involved in this process through limiting IEL precursor differentiation.
- Subjects
CHEMOKINE receptors; LYMPHOCYTES; T cells; DOWNREGULATION; CELL differentiation; RNA sequencing
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-40950-2