Single-Cell RNA Sequencing (scRNA-seq) Identifies L1CAM as a Key Mediator between Epithelial Tuft Cell and Innate Lymphoid Cell in the Colon of Hnrnp I Knockout Mice.
Biomedicines
; 11(10)2023 Oct 09.
Article
em En
| MEDLINE
| ID: mdl-37893107
ABSTRACT
(1) Background:
Knockout (KO) of heterogeneous nuclear ribonucleoprotein I (Hnrnp I) in mouse intestinal epithelial cells (IECs) induced a severe inflammatory response in the colon, followed by hyperproliferation. This study aimed to investigate the epithelial lineage dynamics and cell-cell communications that underlie inflammation and colitis. (2)Methods:
Single cells were isolated from the colons of wildtype (WT) and KO mice and used in scRNA-seq. Whole colons were collected for immunofluorescence staining and cytokine assays. (3)Results:
from scRNA-seq, the number of DCLK1 + colonic tuft cells was significantly higher in the Hnrnp I KO mice compared to the WT mice. This was confirmed by immunofluorescent staining of DCLK1. The DCLK1 + colonic tuft cells in KO mice developed unique communications with lymphocytes via interactions between surface L1 cell adhesion molecule (L1CAM) and integrins. In the KO mice colons, a significantly elevated level of inflammatory cytokines IL4, IL6, and IL13 were observed, which marks type-2 immune responses directed by group 2 innate lymphoid cells (ILC2s). (4)Conclusions:
This study demonstrates one critical cellular function of colonic tuft cells, which facilitates type-2 immune responses by communicating with ILC2s via the L1CAM-integrins interaction. This communication promotes pro-inflammatory signaling pathways in ILC2, leading to the increased secretion of inflammatory cytokines.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article