Single-Cell Transcriptomics Reveals CCL3⁺ Classical Monocyte Subset Linked to Autoimmune Pathogenesis

Area of Science:

• Immunology
• Genomics
• Pathogenesis of Autoimmune Diseases

Background:

• Mononuclear macrophage differentiation states are critical in autoimmune disease development.
• Understanding immune cell heterogeneity is key to advancing autoimmune disease treatment.

Purpose of the Study:

• To characterize shared and disease-specific alterations in mononuclear macrophages across six autoimmune diseases.
• To identify novel immune subsets involved in autoimmune pathogenesis.
• To refine clinical treatment strategies for autoimmune diseases.

Main Methods:

• Integrated single-cell RNA sequencing (scRNA-seq) data from six autoimmune diseases.
• Analyzed 350,043 peripheral blood immune cells from patients and healthy controls.
• Validated findings using flow cytometry, immunohistochemical staining, and immunofluorescence.

Main Results:

• Identified fifteen mononuclear phagocyte subpopulations, including a novel CCL3+ classical monocyte (cMo) subset.
• CCL3+ cMo cells were co-amplified in Behçet's disease, juvenile dermatomyositis, primary Sjogren's syndrome, relapsing-remitting multiple sclerosis, and systemic lupus erythematosus.
• These cells exhibit M1-like inflammatory characteristics, high chemotaxis, and crosstalk with CD8+ T cells.

Conclusions:

• Delineated the mononuclear phagocyte landscape in autoimmune diseases.
• Revealed CCL3+ cMo as a commonly amplified immune subset associated with multiple autoimmune diseases.
• Nominated CCL3+ cMo as a potential therapeutic target for autoimmune conditions.