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CCL25/CCR9 interactions regulate the function of iNKT cells in oxazolone-induced colitis in mice.

Zhu S, Bing Y, Wang X, Yu Q, Wang Y, Xu S, Song L, Wang X, Xia B, Zhu Y, Zhou R - PLoS ONE (2014)

Bottom Line: The production of pro-inflammatory cytokines was significantly increased, especially interleukin 4 (IL-4), IL-10 and IL-13.We observed significantly increased CCR9 expression on iNKT cells.Furthermore, we found an increased iNKT population and enhanced chemotaxis during oxazolone-induced colitis.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P. R. China; The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, Hubei, P. R. China.

ABSTRACT

Background: Natural killer T (NKT) cells share phenotypic and functional properties with both conventional natural killer cells and T cells. These cells might have an important role in the pathogenesis of ulcerative colitis (UC). The interaction of chemokine ligand 25 (CCL25) with chemokine receptor 9 (CCR9) is involved in gut-specific migration of leukocytes and induces regulatory T cells (Tregs) to migrate to the intestine in chronic ileitis.

Methodology/findings: In UC patients, NKT receptor CD161, CCL25, and CCR9 expression levels were evaluated by qRT-PCR. A murine model of oxazolone-induced colitis was induced in BALB/c mice. The mRNA levels of NK1.1, CCL25 and CCR9, and pro-inflammatory cytokines in mice were evaluated. The CCR9 expression on Type I or invariant NKT (iNKT) cells, and the iNKT cells chemotaxis are observed according to flow cytometry. NKT receptor CD161, CCL25 and CCR9 expression levels were significantly increased in UC patients. And, the mRNA expression levels of NK1.1, CCL25 and CCR9 were increased in oxazolone-induced colitis in mice. The production of pro-inflammatory cytokines was significantly increased, especially interleukin 4 (IL-4), IL-10 and IL-13. We observed significantly increased CCR9 expression on iNKT cells. Furthermore, we found an increased iNKT population and enhanced chemotaxis during oxazolone-induced colitis.

Conclusions/significance: Our study suggests that CCL25/CCR9 interactions may promote the induction and function of iNKT cells during oxazolone-induced colitis. These findings may have important implications for UC treatment and suggest a role for CCR9 inhibitors.

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Related in: MedlinePlus

Expression of CD161, CCL25 and CCR9 in UC and healthy controls.The mRNA levels of CD161 (A), CCL25 (B) and CCR9 (C) were significantly increased in the UC patients compared to the healthy controls. n = 10 per group, *p<0.05 versus the healthy controls. D and E. CD161 mRNA expression was positively correlated with CCL25 mRNA and CCR9 mRNA expression. F. The mRNA level of CCR9 had a positive correlation with the mRNA level of CCL25. Each data point represents one colonic biopsy specimen in each panel, and each panel includes data from all colonic biopsy specimens in our experiments. Different symbols are used for UC patients and healthy controls in each panel. Data were analyzed by Pearson’s correlation coefficient.
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pone-0100167-g001: Expression of CD161, CCL25 and CCR9 in UC and healthy controls.The mRNA levels of CD161 (A), CCL25 (B) and CCR9 (C) were significantly increased in the UC patients compared to the healthy controls. n = 10 per group, *p<0.05 versus the healthy controls. D and E. CD161 mRNA expression was positively correlated with CCL25 mRNA and CCR9 mRNA expression. F. The mRNA level of CCR9 had a positive correlation with the mRNA level of CCL25. Each data point represents one colonic biopsy specimen in each panel, and each panel includes data from all colonic biopsy specimens in our experiments. Different symbols are used for UC patients and healthy controls in each panel. Data were analyzed by Pearson’s correlation coefficient.

Mentions: A recent study demonstrated that NKT cells were originally determined based on their expression of NK-like markers such as CD161 (NK1.1) marker in UC [28]. Compared to the healthy controls, UC patients had mRNA levels of CD161, CCL25 and CCR9 that were significantly increased by 3-fold (0.11±0.04 vs. 0.04±0.02, p = 0.037), 31-fold (4.05±3.57 vs. 0.13±0.21, p = 0.001) and 46-fold (10.56±2.87 vs. 0.23±0.32, p<0.001), respectively (Figure 1A, B, C). The level of CD161 mRNA expression was significantly positively correlated with the levels of the CCL25 (r = 0.529, p = 0.008) and CCR9 (r = 0.900, p<0.001) mRNA expression (Figures 1D and E). As shown in Figure 1F, the level of CCR9 mRNA expression was significantly positively correlated with the levels of CCL25 mRNA expression (r = 0.528, p = 0.008) in all of the colonic biopsy specimens tested. These results showed that CD161, CCL25 and CCR9 expression levels were remarkably increased in UC patients and suggest that CCL25/CCR9 interactions have a positive correlation with NKT cells in the pathogenesis of UC.


CCL25/CCR9 interactions regulate the function of iNKT cells in oxazolone-induced colitis in mice.

Zhu S, Bing Y, Wang X, Yu Q, Wang Y, Xu S, Song L, Wang X, Xia B, Zhu Y, Zhou R - PLoS ONE (2014)

Expression of CD161, CCL25 and CCR9 in UC and healthy controls.The mRNA levels of CD161 (A), CCL25 (B) and CCR9 (C) were significantly increased in the UC patients compared to the healthy controls. n = 10 per group, *p<0.05 versus the healthy controls. D and E. CD161 mRNA expression was positively correlated with CCL25 mRNA and CCR9 mRNA expression. F. The mRNA level of CCR9 had a positive correlation with the mRNA level of CCL25. Each data point represents one colonic biopsy specimen in each panel, and each panel includes data from all colonic biopsy specimens in our experiments. Different symbols are used for UC patients and healthy controls in each panel. Data were analyzed by Pearson’s correlation coefficient.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061108&req=5

pone-0100167-g001: Expression of CD161, CCL25 and CCR9 in UC and healthy controls.The mRNA levels of CD161 (A), CCL25 (B) and CCR9 (C) were significantly increased in the UC patients compared to the healthy controls. n = 10 per group, *p<0.05 versus the healthy controls. D and E. CD161 mRNA expression was positively correlated with CCL25 mRNA and CCR9 mRNA expression. F. The mRNA level of CCR9 had a positive correlation with the mRNA level of CCL25. Each data point represents one colonic biopsy specimen in each panel, and each panel includes data from all colonic biopsy specimens in our experiments. Different symbols are used for UC patients and healthy controls in each panel. Data were analyzed by Pearson’s correlation coefficient.
Mentions: A recent study demonstrated that NKT cells were originally determined based on their expression of NK-like markers such as CD161 (NK1.1) marker in UC [28]. Compared to the healthy controls, UC patients had mRNA levels of CD161, CCL25 and CCR9 that were significantly increased by 3-fold (0.11±0.04 vs. 0.04±0.02, p = 0.037), 31-fold (4.05±3.57 vs. 0.13±0.21, p = 0.001) and 46-fold (10.56±2.87 vs. 0.23±0.32, p<0.001), respectively (Figure 1A, B, C). The level of CD161 mRNA expression was significantly positively correlated with the levels of the CCL25 (r = 0.529, p = 0.008) and CCR9 (r = 0.900, p<0.001) mRNA expression (Figures 1D and E). As shown in Figure 1F, the level of CCR9 mRNA expression was significantly positively correlated with the levels of CCL25 mRNA expression (r = 0.528, p = 0.008) in all of the colonic biopsy specimens tested. These results showed that CD161, CCL25 and CCR9 expression levels were remarkably increased in UC patients and suggest that CCL25/CCR9 interactions have a positive correlation with NKT cells in the pathogenesis of UC.

Bottom Line: The production of pro-inflammatory cytokines was significantly increased, especially interleukin 4 (IL-4), IL-10 and IL-13.We observed significantly increased CCR9 expression on iNKT cells.Furthermore, we found an increased iNKT population and enhanced chemotaxis during oxazolone-induced colitis.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P. R. China; The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, Hubei, P. R. China.

ABSTRACT

Background: Natural killer T (NKT) cells share phenotypic and functional properties with both conventional natural killer cells and T cells. These cells might have an important role in the pathogenesis of ulcerative colitis (UC). The interaction of chemokine ligand 25 (CCL25) with chemokine receptor 9 (CCR9) is involved in gut-specific migration of leukocytes and induces regulatory T cells (Tregs) to migrate to the intestine in chronic ileitis.

Methodology/findings: In UC patients, NKT receptor CD161, CCL25, and CCR9 expression levels were evaluated by qRT-PCR. A murine model of oxazolone-induced colitis was induced in BALB/c mice. The mRNA levels of NK1.1, CCL25 and CCR9, and pro-inflammatory cytokines in mice were evaluated. The CCR9 expression on Type I or invariant NKT (iNKT) cells, and the iNKT cells chemotaxis are observed according to flow cytometry. NKT receptor CD161, CCL25 and CCR9 expression levels were significantly increased in UC patients. And, the mRNA expression levels of NK1.1, CCL25 and CCR9 were increased in oxazolone-induced colitis in mice. The production of pro-inflammatory cytokines was significantly increased, especially interleukin 4 (IL-4), IL-10 and IL-13. We observed significantly increased CCR9 expression on iNKT cells. Furthermore, we found an increased iNKT population and enhanced chemotaxis during oxazolone-induced colitis.

Conclusions/significance: Our study suggests that CCL25/CCR9 interactions may promote the induction and function of iNKT cells during oxazolone-induced colitis. These findings may have important implications for UC treatment and suggest a role for CCR9 inhibitors.

Show MeSH
Related in: MedlinePlus