Macrophages May Promote Progression of Systemic Sclerosis, Study Shows

Macrophages May Promote Progression of Systemic Sclerosis, Study Shows
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Macrophages

New research establishes a link between immune cells, known as macrophages, and systemic sclerosis progression. The study showed that gene expression in macrophages from systemic sclerosis patients is altered, including higher activity of the susceptibility gene GSDMA.

The study “Changes in macrophage transcriptome associate with systemic sclerosis and mediate GSDMA contribution to disease risk” was published in the journal Annals of Rheumatic Diseases.

Previous studies have identified several genes linked to an increased susceptibility to systemic sclerosis, but which cells carried these variants remained poorly understood.

Now, an international collaboration identified a group of immune cells – macrophages – as potential perpetrators of disease progression.

Researchers performed a genetic and RNA sequencing analysis in macrophages from 57 systemic sclerosis patients and from 15 healthy people (controls), and looked at changes in gene expression that occurred especially in the systemic sclerosis cells.

The team found a different gene activity pattern between systemic sclerosis and healthy controls.

“We identified 602 genes upregulated 
[higher expression] and downregulated [lower expression] in SSc [systemic sclerosis] macrophages that were significantly enriched for genes previously implicated in SSc susceptibility,” the researchers wrote.

The analysis also revealed an unknown role for macrophages in having a higher expression of the GSDMA and GRB10 genes, which were previously identified as associated with systemic sclerosis susceptibility.

“Investigating how genetic variation is responsible for systemic sclerosis is a colossal task. By looking at immune cells such as macrophages, we can generate specific hypotheses that will allow us to understand how these cells cause damage,” Jacques Behmoaras, co-lead author of the study said in a press release. Behmoaras is a principal investigator at the Centre for Complement and Inflammation Research, Imperial College London,

“In the long quest for finding therapies for systemic sclerosis, our findings have implications for understanding the genetic basis of the disease, and we believe our discovery will prompt detailed functional studies in macrophages and immune cells, hopefully providing a starting point to develop greatly needed treatments for this disease” added Enrico Petretto, PhD, study co-lead author and associate professor at Duke-NUS Medical School (Duke-NUS).

The study also revealed hundreds of genes that previously were not known to be associated with systemic sclerosis.

 

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