A specific inflammatory suppression fibroblast subpopulation characterized by MHCII expression in human dilated...

Area of Science:

• Cardiovascular Biology
• Immunology
• Single-cell Genomics

Background:

• Dilated cardiomyopathy (DCM) is a major cause of heart failure, often necessitating transplantation.
• Fibroblasts are key players in the DCM's fibro-inflammatory microenvironment.
• The cellular diversity and immune interactions of fibroblasts in DCM remain poorly understood.

Purpose of the Study:

• To identify novel fibroblast subpopulations and their roles in the DCM microenvironment.
• To investigate intercellular communication between fibroblasts and immune cells in DCM.
• To explore the diagnostic and prognostic potential of identified fibroblast signatures.

Main Methods:

• Integrative analysis of single-cell RNA sequencing (ScRNA-Seq) data from human heart tissues (healthy and DCM).
• Immunofluorescence staining to confirm the presence of identified fibroblast subtypes.
• Analysis of intercellular communication pathways and gene expression signatures.
• Validation using bulk RNA sequencing datasets.

Main Results:

• Identification of a novel fibroblast subtype, antigen-presenting fibroblasts (apFBs), characterized by MHCII gene expression.
• apFBs exhibit high expression of IFN-γ-responsive genes and JAK-STAT pathway activity.
• Upregulation of anti-inflammatory ligand-receptor pairs (TGFB-TGFR, CLEC2B-KLRB1, CD46-JAG1) in apFB-CD4+ T cell communication in DCM.
• apFB signature correlates with immunosuppression and shows diagnostic/prognostic value.

Conclusions:

• A novel MHCII-expressing fibroblast subpopulation (apFBs) has been identified in DCM.
• These apFBs play a role in suppressing inflammation within the DCM microenvironment.
• Findings provide insights into DCM's fibro-inflammatory landscape and suggest apFBs as a therapeutic target.