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Expression of IL33 and IL35 in oral lichen planus

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Abstract

Oral lichen planus (OLP) is a complex immunological disorder, mediated in part by the release of cytokines by activated T-cells. Recently, the role of novel cytokines including IL33 and IL35 has been described in various chronic inflammatory diseases. IL33, a member of the IL-1 superfamily of cytokines, functions as an ‘alarmin’ released after cell necrosis to alert the immune system to tissue damage or stress. IL35, a member of IL12 cytokine family, is produced by regulatory T-cells and suppresses the immune response. The expression of IL33 and IL35 is yet to be investigated in OLP. The aim of this study was to determine the presence and topographical distribution of IL33 and IL35 in OLP using immunohistochemistry and quantitative real-time reverse transcriptase polymerase chain reaction (qPCR). For IHC, formalin-fixed paraffin-embedded archival specimens of OLP (n = 10) and a non-specific inflammatory (NSI) control group (n = 9) were used. A double-labelling immunofluorescence technique was used to determine the expression of IL33 and IL35 on CD3+ T-cells. In addition, 12 fresh tissue samples (OLP n = 6 and NSI controls n = 6) were used to determine the gene expression of IL33 and EBI3 (one chain of the dimeric IL35). Quantitative and qualitative analysis was performed with statistical significance set at p < 0.05. IHC showed positive immunostaining with IL33 and IL35 in both OLP and NSI. Comparison of the numbers of IL33+ and IL35+ cells in OLP and NSI did not show any significant difference. In OLP, there were significantly more IL33+ cells in the deeper connective tissue region than at the epithelial–connective tissue interface. Interestingly, all IL35+ cells observed in both OLP and NSI tissues showed ovoid/plasmacytoid morphology. Double-labelling immunofluorescence showed that IL33 and IL35 expression was not localized within CD3+ T-cells. The gene expression experiments showed significantly higher expression of EBI3 (fold regulation 14.02) in OLP when compared to the inflammatory controls. IL33 gene expression was not different between the groups. However, within the OLP tissues, there was a significantly higher expression of IL33 than EBI3. Our data demonstrate the expression of IL33 and IL35 in OLP lesions. Further studies are needed to understand the functional role of these cytokines in OLP pathogenesis.

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Funding

The project was funded by a New Zealand Dental Association Research Foundation grant and this assistance is gratefully acknowledged.

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Authors and Affiliations

  1. Faculty of Dentistry, Sir John Walsh Research Institute, University of Otago, 310 Great King Street, Dunedin, 9054, New Zealand

    L. R. Javvadi, V. P. B. Parachuru, T. J. Milne, G. J. Seymour & Alison M. Rich

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  1. L. R. Javvadi
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  2. V. P. B. Parachuru
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  3. T. J. Milne
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  4. G. J. Seymour
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Correspondence to Alison M. Rich.

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No authors have any conflicts of interest with regard to this manuscript.

Ethical approval

The project received ethical approval from the University of Otago Human Ethics Committee (Reference number H13/052) and all patients whose tissue was used had consented to the use their residual tissue, after diagnostic investigations had been completed, for research purposes.

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Javvadi, L.R., Parachuru, V.P.B., Milne, T.J. et al. Expression of IL33 and IL35 in oral lichen planus. Arch Dermatol Res 310, 431–441 (2018). https://doi.org/10.1007/s00403-018-1829-5

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  • DOI: https://doi.org/10.1007/s00403-018-1829-5

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