The NOTCH-HES-1 Axis is Involved in Promoting Th22 Cell Differentiation

Overview

Journal Cell Mol Biol Lett

Publisher Biomed Central

Specialties Biochemistry
Cell Biology
Molecular Biology

Date 2021 Feb 24

PMID 33622250

Citations 12

Authors

Chong Zeng

Zhongbao Shao

Zibo Wei

Jie Yao

Weidong Wang

Liang Yin

Huixian YangOu

Dan Xiong

Affiliations

Soon will be listed here.

Abstract

Background: NOTCH signaling has been shown to play a role in the production of interleukin-22 (IL-22) by CD4 T cells. Multiple T-helper (Th) cell populations secrete IL-22. Th22 (CD4IL22IFNγIL17A) cells are a subgroup of CD4 effector T cells that primarily generate IL-22. The regulatory mechanisms of the NOTCH signaling pathway involved in differentiation of the Th22 cell subset have not been completely elucidated. This study aimed to further explore the involvement of NOTCH signaling in Th22 differentiation.

Methods: In vitro combination of IL-6, IL-23, and tumor necrosis factor-α (TNF-α) treatment with naïve CD4 T cells established the Th22 cell induced model. NOTCH signaling was activated by jagged-1 and inhibited by (2S)-N-[(3,5-difluorophenyl) acetyl]-L-alanyl-2-phenyl]glycine 1,1-dimethylethyl ester (DAPT). HES-1 siRNA and HES-1 vector were employed to knock down and induce overexpression of HES-1 to investigate the effect of NOTCH signaling on the differentiation of CD4T cells into Th22 cells.

Results: We observed that the proportion of Th22 cells, along with Hes-1, Ahr, and Il-22 mRNA and protein expression, was increased by both jagged-1 and overexpression of HES-1. On the other hand, after the combined cytokine treatment of cells, and exposure to jagged-1 and DAPT or HES-1 siRNA, there was a decrease in the Th22 cell proportion, mRNA and protein expression of HES-1, AHR, and IL-22.

Conclusions: Our study demonstrates that HES-1 enhancement in AHR and IL-22 up-regulation of NOTCH signaling can promote the skewing of naïve CD4T cells toward Th22 cells. Also, the results of our study show that HES-1 is a crucial factor in Th22 cell differentiation.

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