Heat shock protein 90 complex from oral lichen planus lesion induces T cells polarization via activation of dendritic cells

Abstract

Background

Oral lichen planus (OLP) is commonly accepted as an interface mucositis. The immunogen from keratinocytes is considered as the agonist priming the topical immunity. Our previous study has identified increased dendritic cell (DC) infiltration and TLR9 expression in OLP lesions. Heat shock protein 90 (HSP90) has been widely considered as an autoantigen and TLR9 agonist that could activate DCs. However, the significance and impact of HSP90 as an immunogen in OLP remain unclear.

Objective

To investigate the effects of the HSP90 complex from OLP lesion tissues on DCs activation and the polarization of naïve T cells.

Methods

The expression pattern of HSP90 in OLP lesions and healthy control mucosa was evaluated by single-cell RNA sequence, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and immunoblotting. The HSP90 complex was further extracted by immunoprecipitation from the OLP lesions and healthy control mucosa as the agonist of DCs. The peripheral DCs were collected and stimulated with the extractives. When challenged, DCs’ expression of interferon-alpha and MHC molecules was detected by flow cytometry. Hence, after cocultured with pre-stimulated DCs, polarization of naïve T cells was investigated by cytokines profile analysis.

Results

HSP90 expression was significantly greater in the lamina propria of OLP lesion and closely related with lymphocyte infiltration. The HSP90 complex in OLP lesion tissues activated DCs via TLR9 and increased their interferon-α secretion and MHC II expression. Prestimulated DCs increased the proportion of Th17 cells.

Conclusions

The HSP90 complex isolated from OLP lesion tissue activated a TLR9/interferon-α pathway of DC and further promoted the polarization of naïve T cells towards Th17 immunity.