Downregulation of chemokine receptor 9 facilitates CD4+CD8αα+ intraepithelial lymphocyte development-Reference-Cited by-同舟云学术

Downregulation of chemokine receptor 9 facilitates CD4+CD8αα+ intraepithelial lymphocyte development

Published:2023-08-24 Issue:1 Volume:14 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Ono Keiko,Sujino Tomohisa^ORCID,Miyamoto Kentaro,Harada Yosuke,Kojo Satoshi^ORCID,Yoshimatsu Yusuke,Tanemoto Shun,Koda Yuzo^ORCID,Zheng Jiawen,Sayama Kazutoshi,Koide Tsuyoshi^ORCID,Teratani Toshiaki,Mikami Yohei^ORCID,Takabayashi Kaoru,Nakamoto Nobuhiro^ORCID,Hosoe Naoki,London Mariya,Ogata Haruhiko,Mucida Daniel^ORCID,Taniuchi Ichiro^ORCID,Kanai Takanori

Abstract

AbstractIntestinal 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

Link

https://www.nature.com/articles/s41467-023-40950-2.pdf

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