TABLE 2.

The role of CCR9/CCL25 in inflammatory-associated diseases.

Inflammation disease	Expression of CCR9 or CCL25	Model	Effect of CCR9/CCL25	Outcome	References
Myocardial infarction	Increased CCR9	Model of myocardial infarction induced by ligation of left anterior descending coronary artery of CCR9–/– and CCR9+/+ mice	Down-regulation of CCR9 expression can improve survival rate, left ventricular dysfunction, cardiac function, reduce infarct size, meanwhile, significantly attenuate the apoptosis of cardiomyocytes, and inhibit the inflammatory response after myocardial infarction.	CCR9/CCL25 axis may play an important role in inflammatory cell infiltration and cardiac remodeling after myocardial infarction.	Huang et al., 2016
Hepatitis	–	Concanavalin A-induced murine acute liver injury and human acute hepatitis	Macrophages expressing CCR9+CD11b+ aggravated liver damage through production of inflammatory cytokines and the promotion of Th1 cell development.	Inflammatory macrophages originated from bone marrow and became locally differentiated and proliferated by interaction with hepatic stellate cells via knocking out CCR9 gene during acute liver injury.	Amiya et al., 2016; Nakamoto, 2016
Rheumatoid arthritis	Increased CCR9 and CCL25	In the synovium of RA and non-RA patients	Stimulation with CCL25 increased IL-6 and MMP-3 production from RA fibroblast-like synoviocytes, and also increased IL-6 and TNF-α production from peripheral blood monocytes. Collagen-induced arthritis was suppressed in CCR9-deficient mice.	The interaction between CCL25 and CCR9 may promote cell infiltration and production of inflammatory mediator in RA synovial tissues.	Yokoyama et al., 2014
Inflammatory bowel disease	Increased CCR9 and CCL25	DSS-induced acute colitis	CCR9–/– mice are more susceptible to DSS colitis than WT littermate controls as shown by higher mortality, increased IBD score, and delayed recovery. During recovery, the CCR9–/– colonic mucosa is characterized by the accumulation of activated macrophages and elevated levels of Th1/Th17 inflammatory cytokines.	CCR9/CCL25 interaction regulates the inflammatory immune response of the intestinal mucosa by balancing different dendritic cell subsets.	Wurbel et al., 2011
Inflammatory bowel disease	Increased CCR9 and CCL25	DSS-induced acute colitis	The mice lacking the interaction of CCR9/CCL25 showed enhanced adhesion promoting ability of coli after the transfer of naive T cells, and regulated the pro-inflammatory and anti-inflammatory subgroups of cDC.	CCR9/CCL25 interactions have protection against large intestinal inflammation in chronic colitis.	Wurbel et al., 2014
Asthma	Increased CCL25	OVA-induced model of allergic inflammation within CCR9 deficient mice	In challenged CCR9-deficient mice, cell recruitment was impaired at peribronchial and perivenular levels. OVA administration in CCR9-deficient mice leads to a less inflammatory cell recruitment, which modifies the expression of IL-10, CCL11, and CCL25 after OVA challenge.	CCR9 and CCL25 expressions are induced in the early stages of airway inflammation and they have an important role in modulating eosinophils and lymphocytes recruitment at the first stages of inflammatory process.	Lopez-Pacheco et al., 2016
Asthma	Increased CCR9	NKT cells	In patients with allergic asthma, the CCR9/CCL25 binding method selectively induces chemotaxis of NKT cells. And NKT cells may be in direct contact with CD3+ T cells, polarizing them to a Th2 bias.	CCR9/CCL25 signal can interact with CD226 signaling to activate asthmatic NKT cells, leading to airway hyperresponsiveness and inflammation, aggravating asthma.	Sen et al., 2005

Compelling evidence has indicated that alterations of CCR9 or CCL25 expression are also involved in inflammatory-associated diseases, including myocardial infarction, hepatitis, rheumatoid arthritis, inflammatory bowel disease, and asthma.

CCR9, C-C chemokine receptor 9; CCL25, C-C chemokine ligand 25; RA, rheumatoid arthritis; IBD, inflammatory bowel disease; DSS, dextran sulfate sodium; DCs, dendritic cells; IL-6, interleukin-6; IL-10, interleukin-10; MMP3, matrix metalloproteinase-3; TNF-α, tumor necrosis factor-α; NKT, natural killer T; DCs, dendritic cells; Th, helper T.