Transcriptomic profiling of scleroderma monocytes reveals links with cardiovascular complications, implicating Notch and interferon pathways
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Systemic sclerosis monocytes show distinct inflammatory profiles linked to organ damage. Elevated interferon activity correlates with cardiac dysfunction, suggesting new therapeutic targets for systemic sclerosis complications.
Area Of Science
- Immunology
- Genomics
- Cardiology
Background
- Monocytes and macrophages are key drivers of inflammation and fibrosis in systemic sclerosis.
- Understanding monocyte gene expression is crucial for identifying systemic sclerosis complications and therapeutic targets.
Purpose Of The Study
- To investigate gene expression profiles of monocytes in systemic sclerosis patients.
- To explore the relationship between these profiles and disease complications.
- To identify novel therapeutic targets for systemic sclerosis.
Main Methods
- Bulk RNA sequencing was performed on monocytes from 48 systemic sclerosis patients and 15 controls.
- Differential gene expression, hierarchical clustering, and pathway analysis were conducted.
- Interferon signature score (IFN6) and correlations with clinical features, including global longitudinal strain (GLS), were analyzed.
Main Results
- Four monocyte gene expression subgroups were identified: two inflammatory and two non-inflammatory.
- Inflammatory subgroups showed high interferon-related gene expression and were associated with pulmonary hypertension and cardiac involvement.
- Elevated IFN6 correlated significantly with impaired GLS, and Notch signaling was enriched in genes linked to cardiac dysfunction.
Conclusions
- A mechanistic link between interferon activity, Notch signaling, and cardiac complications in systemic sclerosis is proposed.
- These findings offer new insights into systemic sclerosis pathogenesis.
- Potential novel therapeutic targets for systemic sclerosis have been identified.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
Overview
In response to tissue injury and infection, mast cells initiate inflammation. Mast cells release chemicals that increase the permeability of adjacent blood capillaries and attract additional immune cells to the wound or site of infection. Neutrophils are phagocytic leukocytes that exit the bloodstream and engulf invading microbes. Blood clotting platelets seal the wound and fibers create a scaffold for wound healing. Macrophages engulf aging neutrophils to end the acute inflammatory...