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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

Production of TNF-α, IFN-γ, IL-17, IL-4, IL-10 and IL-13 during oxazolone-induced colitis.The levels of TNF-α (A), IFN-γ (B), IL-17 (C), IL-4 (D), IL-10 (E) and IL-13 (F) were significantly increased in the OXA mice compared to the ETOH mice. n = 10 per group, *p<0.05 versus the control mice, and #p<0.05 versus the ETOH mice.
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pone-0100167-g005: Production of TNF-α, IFN-γ, IL-17, IL-4, IL-10 and IL-13 during oxazolone-induced colitis.The levels of TNF-α (A), IFN-γ (B), IL-17 (C), IL-4 (D), IL-10 (E) and IL-13 (F) were significantly increased in the OXA mice compared to the ETOH mice. n = 10 per group, *p<0.05 versus the control mice, and #p<0.05 versus the ETOH mice.

Mentions: To assess tissue inflammation, we analyzed the Th1/Th2/Th17 cytokines in intestinal tissue homogenates. As shown in Figure 5, the production of TNF-α, IFN-γ, IL-17, IL-4, IL-10 and IL-13 in OXA mice was significantly increased compared to the control and ETOH mice.


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)

Production of TNF-α, IFN-γ, IL-17, IL-4, IL-10 and IL-13 during oxazolone-induced colitis.The levels of TNF-α (A), IFN-γ (B), IL-17 (C), IL-4 (D), IL-10 (E) and IL-13 (F) were significantly increased in the OXA mice compared to the ETOH mice. n = 10 per group, *p<0.05 versus the control mice, and #p<0.05 versus the ETOH mice.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0100167-g005: Production of TNF-α, IFN-γ, IL-17, IL-4, IL-10 and IL-13 during oxazolone-induced colitis.The levels of TNF-α (A), IFN-γ (B), IL-17 (C), IL-4 (D), IL-10 (E) and IL-13 (F) were significantly increased in the OXA mice compared to the ETOH mice. n = 10 per group, *p<0.05 versus the control mice, and #p<0.05 versus the ETOH mice.
Mentions: To assess tissue inflammation, we analyzed the Th1/Th2/Th17 cytokines in intestinal tissue homogenates. As shown in Figure 5, the production of TNF-α, IFN-γ, IL-17, IL-4, IL-10 and IL-13 in OXA mice was significantly increased compared to the control and ETOH mice.

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