Featured Immune Characteristics of Periodontitis and Primary Sjögren's Syndrome Revealed by Single-Cell Transcriptome...

Area of Science:

• Immunology
• Genomics
• Oral Health

Background:

• Periodontitis (PD) and primary Sjögren's syndrome (pSS) are chronic inflammatory conditions impacting oral health.
• Existing research indicates phenotypic and intrinsic links between PD and pSS.
• A high-resolution, single-cell analysis comparing immune cell profiles in PD and pSS was previously lacking.

Purpose of the Study:

• To conduct a comprehensive single-cell transcriptome analysis of immune cell landscapes in periodontitis and primary Sjögren's syndrome.
• To identify shared and distinct immune cell alterations in PD and pSS at the single-cell level.
• To elucidate intercellular communication pathways between myeloid cells and CD8+ naive T cells in these diseases.

Main Methods:

• Integration of single-cell RNA sequencing datasets from peripheral blood mononuclear cells (PBMCs) of healthy controls, PD patients, and pSS patients.
• Cell clustering and subtyping using Seurat, focusing on T/NK, myeloid, and B cell populations.
• Analysis of intercellular communication using NicheNetr to investigate myeloid cell and CD8+ naive T cell interactions.

Main Results:

• Significant downregulation of CD8+ naive T (Tn) cells observed in both PD and pSS compared to healthy controls.
• Distinct alterations in specific cell populations: decreased HLA-DRA+ monocytes in PD and altered immature B cell proportions in both PD and pSS.
• Identification of IL-7/TNFSF11-CDKN1A and BACE2-CDKN1A signaling pathways potentially mediating myeloid cell-induced CD8+ Tn cell exhaustion.

Conclusions:

• This study reveals shared single-cell immune landscape alterations in periodontitis and primary Sjögren's syndrome.
• Common molecular mechanisms, particularly involving myeloid cell-T cell communication, may underlie the pathogenesis of both diseases.
• Provides novel insights into the immunological connections between PD and pSS at an unprecedented resolution.