Heterogeneity and functional diversity of human T cells in periapical lesions

Abstract

Background: Apical periodontitis (AP), is a common inflammatory disorder affecting periradicular destruction and even leads to tooth loss, is a consequence of interactions between immune cells and commensal bacteria. The bacteria pathogens disrupt host signal transduction pathways by their virulence proteins and lipopolysaccharides, activating the release of proinflammatory cytokines by cell members of the immune system. As in other tissues, the recruitment of immune cells in periapical lesions also contributes to initiating the process of tissue impairment and repair after inflammation. However, the precise roles of infiltrating T cells in AP remains mostly limited to immunologic function. Results: Here, we employed single-cell RNA-seq to construct a transcriptomic atlas of 44,746 individual cells in the periapical lesions from 5 AP patients and identify 8 cell types, embracing 4 types of immune cells and non-immune cells. We found 9 subsets of T cells and deciphered cellular heterogeneity of T cells in AP on a functional level by clustering and gene-set enrichment analysis. Lineage tracing unveiled distinct lineage of T cells in AP and predicted relative transcription factors led to cell lineage commitment and function. GSEA analysis revealed multiple biological processes and relevant angiogenesis genes upregulated in T cells of AP compared to healthy gingival. Granzyme A (GZMA)_Coagulation Factor II Thrombin Receptor (F2R) binding was forecasted in AP and pro-angiogenic capacity of GZMA recombinant protein was emphasized by conducting in vitro experiments. Conclusion: Our study has yielded novel insights into the heterogeneity and functional diversity of T cells in periapical lesions, unraveling the potential of T cells in affecting angiogenesis during tissue healing.