TRIM21 promotes inflammation by ubiquitylating NF-κB in T cells of oral lichen planus

Abstract

Background: Oral lichen planus (OLP) is a mucocutaneous inflammatory disease affecting 1% general population. Tripartite motif-containing protein 21 (TRIM21) shows a significant role in OLP. This study aimed to explore the function and mechanism of TRIM21 in T cells of OLP.

Methods: Differential gene expression profile in OLP versus healthy controls (HCs) was constructed by RNA sequencing. Protein expression level and infiltration sites of TRIM21 in OLP were detected by immunoblot, immunohistochemistry, and immunofluorescence. Expression of proinflammatory cytokines and chemokines including IL-6, TNF-α, ICAM1, CXCL1, CXCL8, CXCL9, and CXCL11 in CD3⁺ TRIM21^hi T cells were measured by quantitative real-time polymerase chain reaction analysis. Downstream pathways and substrates of TRIM21 were explored by immunoblot and immunoprecipitation. Whether TRIM21 ubiquitination its substrate and ubiquitination form were tested by ubiquitination assay in vitro.

Results: Compared with HCs, TRIM21 exhibited a higher level in OLP, which expressed mainly in CD3⁺ T lymphocytes in OLP tissues. Overexpressed TRIM21 enhanced the expression of IL-6, TNF-α, CXCL1, CXCL8, CXCL9, and CXCL11 in CD3⁺ T cell line through ubiquitinating nuclear factor-κB (NF-κB) via a lysine 63 (K63) linkage, which eventually activating NF-κB signaling pathway.

Conclusions: In OLP, TRIM21 promoted inflammation through ubiquitylating NF-κB and activating NF-κB signaling pathway.

Keywords: NF-κB signaling pathway; TRIM21; inflammation; oral lichen planus; ubiquitination.