Mitochondria-related genes and metabolic profiles of innate and adaptive immune cells in primary Sjögren’s syndrome

Frontiers in Immunology

Immunology

Yicheng Wu¹  Xiaochun Fei²  Lei Li²  Liting Jiang³  Yiming Gao³  Yi Yang³  Ning Li³  Danyang Luo³  Yulin Ye³  Jiawei Hu³  Naiyan Zeng⁴ 

[1] Core Facility of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Stomatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China;Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China;

关键词: Sjogren’s syndrome;    mitochondria;    mitochondrial metabolism;    immune cell;    transcriptomics;    RNA sequencing;   

DOI  :  10.3389/fimmu.2023.1156774

 received in 2023-02-01, accepted in 2023-06-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundPrimary Sjogren’s syndrome (pSS) is a prototypical systemic autoimmune disease characterised by lymphocyte infiltration and immune-complex deposition in multiple organs. The specific distribution of immune cell populations and their relationship with mitochondria remain unknown.MethodsHistological analysis was performed to assess the specific distribution of innate and adaptive immune cell populations in labial salivary gland (LSG) samples from 30 patients with pSS and 13 patients with non-pSS. The ultrastructural morphometric features of mitochondria within immune cells were observed under the transmission electron microscope (TEM). RNA sequencing was performed on LSG samples from 40 patients with pSS and 7 non-pSS patients. The Single-sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE, and CIBERSORT algorithms and Pearson correlation coefficients were used to examine the relationship between mitochondria-related genes and immune infiltration. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify the mitochondria-specific genes and the related pathways based on the immune cell types.ResultsHE staining revealed a massive infiltration of plasma cells with abundant immunoglobulin protein distributed around phenotypically normal-appearing acinar and ductal tissues of patients with pSS. Immunohistochemical analyses revealed that innate immune cells (macrophages, eosinophils and NK cells) were distributed throughout the glandular tissue. Dominant adaptive immune cell infiltration composed of B cells, CD4+T cells and CD8+ T cells or ectopic lymphoid follicle-like structures were observed in the LSGs of patients with pSS. TEM validated the swelling of mitochondria with disorganised cristae in some lymphocytes that had invaded the glandular tissue. Subsequently, bioinformatic analysis revealed that innate and adaptive immune cells were associated with different mitochondrial metabolism pathways. Mitochondrial electron transport and respiratory chain complexes in the glandular microenvironment were positively correlated with innate immune cells, whereas amino acid and nucleic acid metabolism were negatively correlated with adaptive immune cells. In addition, mitochondrial biogenesis and mitochondrial apoptosis in the glandular microenvironment were closely associated with adaptive immune cells.ConclusionInnate and adaptive immune cells have distinct distribution profiles in the salivary gland tissues of patients with pSS and are associated with different mitochondrial metabolic pathways, which may contribute to disease progression.

【 授权许可】

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Copyright © 2023 Luo, Li, Wu, Yang, Ye, Hu, Gao, Zeng, Fei, Li and Jiang