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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

Schematic model of IL-23/IL-17 axis involved in the pathogenesis of OLP. The whole process is divided into three steps: (1) keratinocytes in OLP lesion produce a large amount of IL-23 via an unknown mechanism; (2) keratinocyte-derived IL-23 may contribute to the accumulation of Th17 cells and the overproduction of IL-17 in the local lesion of OLP; (3) IL-17 reversely induces the keratinocytes to selectively produce various inflammatory mediators, which compose the complex immune network in the inflammatory environment of OLP lesions.
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fig6: Schematic model of IL-23/IL-17 axis involved in the pathogenesis of OLP. The whole process is divided into three steps: (1) keratinocytes in OLP lesion produce a large amount of IL-23 via an unknown mechanism; (2) keratinocyte-derived IL-23 may contribute to the accumulation of Th17 cells and the overproduction of IL-17 in the local lesion of OLP; (3) IL-17 reversely induces the keratinocytes to selectively produce various inflammatory mediators, which compose the complex immune network in the inflammatory environment of OLP lesions.

Mentions: In summary, based on the findings in the present study, we propose a novel model of interaction between the T cells and keratinocytes in the pathogenesis of OLP, in which the IL-23/IL-17 axis is involved (Figure 6). Firstly, keratinocytes in OLP lesion produce a large amount of IL-23 via an unknown mechanism. Next, keratinocyte-derived IL-23 may contribute to the accumulation of Th17 cells and the overproduction of IL-17 in the local lesion of OLP. Subsequently, IL-17 reversely induces the keratinocytes to selectively produce various inflammatory mediators, which compose the complex immune network in the inflammatory environment of OLP lesions. Our results warrant further explorations on the intrinsic mechanisms of the overexpression and the regulatory effects of IL-23/IL-17 axis, as well as its interaction with other signaling pathways, in the OLP lesions. Notably, IL-23/IL-17 axis has been recently considered as a relevant therapeutic target in chronic inflammatory and autoimmune diseases, and several biological agents blocking IL-23 or IL-17 have been currently developed [22, 42]. Therefore, further understanding of the role of IL-23/IL-17 axis in the pathogenesis may contribute to the development of novel therapeutic strategies for the prevention and management of OLP in the future.


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)

Schematic model of IL-23/IL-17 axis involved in the pathogenesis of OLP. The whole process is divided into three steps: (1) keratinocytes in OLP lesion produce a large amount of IL-23 via an unknown mechanism; (2) keratinocyte-derived IL-23 may contribute to the accumulation of Th17 cells and the overproduction of IL-17 in the local lesion of OLP; (3) IL-17 reversely induces the keratinocytes to selectively produce various inflammatory mediators, which compose the complex immune network in the inflammatory environment of OLP lesions.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Schematic model of IL-23/IL-17 axis involved in the pathogenesis of OLP. The whole process is divided into three steps: (1) keratinocytes in OLP lesion produce a large amount of IL-23 via an unknown mechanism; (2) keratinocyte-derived IL-23 may contribute to the accumulation of Th17 cells and the overproduction of IL-17 in the local lesion of OLP; (3) IL-17 reversely induces the keratinocytes to selectively produce various inflammatory mediators, which compose the complex immune network in the inflammatory environment of OLP lesions.
Mentions: In summary, based on the findings in the present study, we propose a novel model of interaction between the T cells and keratinocytes in the pathogenesis of OLP, in which the IL-23/IL-17 axis is involved (Figure 6). Firstly, keratinocytes in OLP lesion produce a large amount of IL-23 via an unknown mechanism. Next, keratinocyte-derived IL-23 may contribute to the accumulation of Th17 cells and the overproduction of IL-17 in the local lesion of OLP. Subsequently, IL-17 reversely induces the keratinocytes to selectively produce various inflammatory mediators, which compose the complex immune network in the inflammatory environment of OLP lesions. Our results warrant further explorations on the intrinsic mechanisms of the overexpression and the regulatory effects of IL-23/IL-17 axis, as well as its interaction with other signaling pathways, in the OLP lesions. Notably, IL-23/IL-17 axis has been recently considered as a relevant therapeutic target in chronic inflammatory and autoimmune diseases, and several biological agents blocking IL-23 or IL-17 have been currently developed [22, 42]. Therefore, further understanding of the role of IL-23/IL-17 axis in the pathogenesis may contribute to the development of novel therapeutic strategies for the prevention and management of OLP in the future.

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