The Roles of CCR9/CCL25 in Inflammation and Inflammation-Associated Diseases.

Xue Wu,Chenxi Lu,Yang Yang,Qiang Wang,Yonglin Liu,Zhi Yang,Chao Deng,Haiying Wang,Meng Sun

doi:10.3389/fcell.2021.686548

Abstract

Chemokine is a structure-related protein with a relatively small molecular weight, which can target cells to chemotaxis and promote inflammatory response. Inflammation plays an important role in aging. C-C chemokine receptor 9 (CCR9) and its ligand C-C chemokine ligand 25 (CCL25) are involved in the regulating the occurrence and development of various diseases, which has become a research hotspot. Early research analysis of CCR9-deficient mouse models also confirmed various physiological functions of this chemokine in inflammatory responses. Moreover, CCR9/CCL25 has been shown to play an important role in a variety of inflammation-related diseases, such as cardiovascular disease (CVD), rheumatoid arthritis, hepatitis, inflammatory bowel disease, asthma, etc. Therefore, the purpose of this review gives an overview of the recent advances in understanding the roles of CCR9/CCL25 in inflammation and inflammation-associated diseases, which will contribute to the design of future experimental studies on the potential of CCR9/CCL25 and advance the research of CCR9/CCL25 as pharmacological inflammatory targets.

Highlights

Chemokines are a large family of small cytokines and generally have low molecular weight ranging from 7 to 15 kDa (Palomino and Marti, 2015)
C chemokine ligand 25 (CCL25) induced significant chemotaxis of peripheral blood monocytes, which was inconsistent between different individuals. These results indicate that monocyte-induced chemokine receptor 9 (CCR9)/CCL25 expression is significantly increased in Rheumatoid arthritis (RA)
The CCR9/CCL25 linkage can directly phosphorylate CD226, and the lack of CD226 can block the Th2 bias effect induced by Natural killer T (NKT) cells. These results indicate that CCR9/CCL25 signaling pathway could interact with CD226 signals to activate asthmatic NKT cells, leading to airway hyperresponsiveness and inflammation, aggravating asthma (Sen et al, 2005)

Summary

Introduction

Chemokines are a large family of small cytokines and generally have low molecular weight ranging from 7 to 15 kDa (Palomino and Marti, 2015). Further study found that CCL25 promoted proliferation and chemotaxis of inflammatory cells that expressed its specific receptor CCR9 (Igaki et al, 2018). They found that macrophages expressing CCR9+CD11b+ aggravated liver damage through production of inflammatory cytokines and the promotion of Th1 cell development during the concanavalin A-induced murine acute liver injury and human acute hepatitis (Nakamoto, 2016).

Results

Conclusion