In:
Nature Communications, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-08-24)
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.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-023-40950-2
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
2553671-0
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