Identification of Tregs-Related Genes with Molecular Patterns in Patients with Systemic Sclerosis Related to ILD

Biomolecules. 2023 Mar 15;13(3):535. doi: 10.3390/biom13030535.

Abstract

Background: Systemic Sclerosis (SSc) is an autoimmune disease that is characterized by vasculopathy, digital ulcers, Raynaud's phenomenon, renal failure, pulmonary arterial hypertension, and fibrosis. Regulatory T (Treg) cell subsets have recently been found to play crucial roles in SSc with interstitial lung disease (ILD) pathogenesis. This study investigates the molecular mechanism of Treg-related genes in SSc patients through bioinformatic analyses.

Methods: The GSE181228 dataset of SSc was used in this study. CIBERSORT was used for assessing the category and proportions of immune cells in SSc. Random forest and least absolute shrinkage and selection operator (LASSO) regression analysis were used to select the hub Treg-related genes.

Results: Through bioinformatic analyses, LIPN and CLEC4D were selected as hub Treg-regulated genes. The diagnostic power of the two genes separately for SSc was 0.824 and 0.826. LIPN was associated with the pathway of aminoacyl-tRNA biosynthesis, Primary immunodeficiency, DNA replication, etc. The expression of CLEC4D was associated with the pathway of Neutrophil extracellular trap formation, PPAR signaling pathway, Staphylococcus aureus infection, Systemic lupus erythematosus, TNF signaling pathway, and Toll-like receptor signaling pathway.

Conclusion: Through bioinformatic analyses, we identified two Treg-related hub genes (LIPN, CLEC4D) that are mainly involved in the immune response and metabolism of Tregs in SSc with ILD. Moreover, our findings may provide the potential for studying the molecular mechanism of SSc with ILD.

Keywords: SSc; Treg cells; genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fibrosis
  • Humans
  • Lung Diseases, Interstitial*
  • Scleroderma, Systemic* / complications
  • Scleroderma, Systemic* / genetics
  • T-Lymphocytes, Regulatory

Supplementary concepts

  • digital ulcers

Grants and funding

This work was supported by the National Natural Science Foundation of China (81960296 and 81871286), Long-term (Youth) Project for Leading Innovative Talents in Jiangxi Province (Lihua Duan), Jiangxi Provincial Clinical Research Center for Rheumatic and Immunologic Diseases (20192BCD42005), Jiangxi Province Medical Leading Discipline Construction Project (Rheumatology), and Provincial and municipal joint construction projects of medical disciplines in Jiangxi Province (Rheumatology).