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Overexpression and selectively regulatory roles of IL-23/IL-17 axis in the lesions of oral lichen planus.

Lu R, Zeng X, Han Q, Lin M, Long L, Dan H, Zhou G, Chen Q - Mediators Inflamm. (2014)

Bottom Line: In addition, the expressions of IL-23 and IL-17 are positively correlated in reticular OLP tissues.Results from in vitro studies revealed that exogenous IL-23 could increase the percentage of Th17 cells and IL-17 production in the CD4+T cells from reticular OLP patients.Furthermore, we also found that exogenous IL-17 could significantly enhance the mRNA expressions of β-defensin-2, -3, CCL-20, IL-8, and TNF-α, but not β-defensin-1, CXCL-9, -10, -11, CCL-5, and IL-6 in human oral keratinocytes.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu 610041, China ; The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, No. 237 Luoyu Road, Wuhan 430079, China.

ABSTRACT
Interleukin- (IL-) 23/IL-17 axis is a newly discovered proinflammatory signaling pathway and has been implicated in the pathogenesis of many chronic inflammatory and immune disorders. Here we investigated whether the IL-23/IL-17 axis was present and functional in the lesions of oral lichen planus (OLP), a chronic inflammatory disease affecting the oral mucosa. Using immunohistochemistry and quantitative PCR, we found that the subunits of IL-23 and IL-17 were overexpressed in OLP lesions than in normal oral mucosa tissues. In addition, the expressions of IL-23 and IL-17 are positively correlated in reticular OLP tissues. Results from in vitro studies revealed that exogenous IL-23 could increase the percentage of Th17 cells and IL-17 production in the CD4+T cells from reticular OLP patients. Furthermore, we also found that exogenous IL-17 could significantly enhance the mRNA expressions of β-defensin-2, -3, CCL-20, IL-8, and TNF-α, but not β-defensin-1, CXCL-9, -10, -11, CCL-5, and IL-6 in human oral keratinocytes. Taken together, our results revealed an overexpression pattern and selectively regulatory roles of IL-23/IL-17 axis in the OLP lesions, suggesting that it may be a pivotal regulatory pathway in the complex immune network of OLP lesions.

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Related in: MedlinePlus

The effect of recombinant (r) IL-23 on the percentage of Th17 cells and IL-17 production in CD4+T cells from OLP patients. (a) Representative scatter plots of CD4+IL-17+ staining in peripheral blood CD4+T cells from OLP patients (n = 10), with or without the stimulation of rIL-23 (20 ng/mL) for 36 h. ((b) and (c)) Paired comparisons of percentages of Th17 cells (b) and the IL-17 content in the culture supernatant (c) in peripheral blood CD4+T cells from OLP patients (n = 10), with or without the stimulation of rIL-23 (20 ng/mL) for 36 h.
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fig4: The effect of recombinant (r) IL-23 on the percentage of Th17 cells and IL-17 production in CD4+T cells from OLP patients. (a) Representative scatter plots of CD4+IL-17+ staining in peripheral blood CD4+T cells from OLP patients (n = 10), with or without the stimulation of rIL-23 (20 ng/mL) for 36 h. ((b) and (c)) Paired comparisons of percentages of Th17 cells (b) and the IL-17 content in the culture supernatant (c) in peripheral blood CD4+T cells from OLP patients (n = 10), with or without the stimulation of rIL-23 (20 ng/mL) for 36 h.

Mentions: Next, we explored the potential role of IL-23 in the production of IL-17 in OLP. Although IL-17 has been recently reported to be produced by various cell types, a CD4+Th cell subset, namely, Th17 cell, is one of its main sources. On the other hand, in the local lesion of OLP, the dense subepithelial inflammatory infiltrate consists predominantly of CD4+Th cells. Therefore, here we focused on the effect of IL-23 to the IL-17 production in CD4+Th cells from 10 OLP patients. We observed that compared to the control group, the stimulation of rIL-23 significantly increased the percentage of CD4+IL-17+ cells (identified as Th17) in CD4+Th cells from OLP patients (Figures 4(a)–4(c)). In addition, the IL-17 content in the culture supernatant of CD4+Th cells also increased under the stimulation of IL-23 than the control group (Figure 4(d)). These data suggest that the overexpression of IL-23 in OLP lesions probably contributes to the induction of Th17 and the production of IL-17.


Overexpression and selectively regulatory roles of IL-23/IL-17 axis in the lesions of oral lichen planus.

Lu R, Zeng X, Han Q, Lin M, Long L, Dan H, Zhou G, Chen Q - Mediators Inflamm. (2014)

The effect of recombinant (r) IL-23 on the percentage of Th17 cells and IL-17 production in CD4+T cells from OLP patients. (a) Representative scatter plots of CD4+IL-17+ staining in peripheral blood CD4+T cells from OLP patients (n = 10), with or without the stimulation of rIL-23 (20 ng/mL) for 36 h. ((b) and (c)) Paired comparisons of percentages of Th17 cells (b) and the IL-17 content in the culture supernatant (c) in peripheral blood CD4+T cells from OLP patients (n = 10), with or without the stimulation of rIL-23 (20 ng/mL) for 36 h.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4121042&req=5

fig4: The effect of recombinant (r) IL-23 on the percentage of Th17 cells and IL-17 production in CD4+T cells from OLP patients. (a) Representative scatter plots of CD4+IL-17+ staining in peripheral blood CD4+T cells from OLP patients (n = 10), with or without the stimulation of rIL-23 (20 ng/mL) for 36 h. ((b) and (c)) Paired comparisons of percentages of Th17 cells (b) and the IL-17 content in the culture supernatant (c) in peripheral blood CD4+T cells from OLP patients (n = 10), with or without the stimulation of rIL-23 (20 ng/mL) for 36 h.
Mentions: Next, we explored the potential role of IL-23 in the production of IL-17 in OLP. Although IL-17 has been recently reported to be produced by various cell types, a CD4+Th cell subset, namely, Th17 cell, is one of its main sources. On the other hand, in the local lesion of OLP, the dense subepithelial inflammatory infiltrate consists predominantly of CD4+Th cells. Therefore, here we focused on the effect of IL-23 to the IL-17 production in CD4+Th cells from 10 OLP patients. We observed that compared to the control group, the stimulation of rIL-23 significantly increased the percentage of CD4+IL-17+ cells (identified as Th17) in CD4+Th cells from OLP patients (Figures 4(a)–4(c)). In addition, the IL-17 content in the culture supernatant of CD4+Th cells also increased under the stimulation of IL-23 than the control group (Figure 4(d)). These data suggest that the overexpression of IL-23 in OLP lesions probably contributes to the induction of Th17 and the production of IL-17.

Bottom Line: In addition, the expressions of IL-23 and IL-17 are positively correlated in reticular OLP tissues.Results from in vitro studies revealed that exogenous IL-23 could increase the percentage of Th17 cells and IL-17 production in the CD4+T cells from reticular OLP patients.Furthermore, we also found that exogenous IL-17 could significantly enhance the mRNA expressions of β-defensin-2, -3, CCL-20, IL-8, and TNF-α, but not β-defensin-1, CXCL-9, -10, -11, CCL-5, and IL-6 in human oral keratinocytes.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu 610041, China ; The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, No. 237 Luoyu Road, Wuhan 430079, China.

ABSTRACT
Interleukin- (IL-) 23/IL-17 axis is a newly discovered proinflammatory signaling pathway and has been implicated in the pathogenesis of many chronic inflammatory and immune disorders. Here we investigated whether the IL-23/IL-17 axis was present and functional in the lesions of oral lichen planus (OLP), a chronic inflammatory disease affecting the oral mucosa. Using immunohistochemistry and quantitative PCR, we found that the subunits of IL-23 and IL-17 were overexpressed in OLP lesions than in normal oral mucosa tissues. In addition, the expressions of IL-23 and IL-17 are positively correlated in reticular OLP tissues. Results from in vitro studies revealed that exogenous IL-23 could increase the percentage of Th17 cells and IL-17 production in the CD4+T cells from reticular OLP patients. Furthermore, we also found that exogenous IL-17 could significantly enhance the mRNA expressions of β-defensin-2, -3, CCL-20, IL-8, and TNF-α, but not β-defensin-1, CXCL-9, -10, -11, CCL-5, and IL-6 in human oral keratinocytes. Taken together, our results revealed an overexpression pattern and selectively regulatory roles of IL-23/IL-17 axis in the OLP lesions, suggesting that it may be a pivotal regulatory pathway in the complex immune network of OLP lesions.

Show MeSH
Related in: MedlinePlus