Dysferlin promotes inflammatory macrophage responses in cells

In laboratory experiments using macrophage models, human CD14-positive cells, and mice, researchers examined the immune role of dysferlin, a protein best known for repairing skeletal muscle membranes. Dysferlin levels rose during monocyte-to-macrophage differentiation. In cellular tests, dysferlin promoted inflammatory macrophage responses, including cytokine production and cell migration. It also enhanced calcium influx and STAT1-associated signalling, whereas knocking down dysferlin or blocking calcium entry suppressed these effects. Dysferlin expression increased with aging in human CD14-positive cells and in mouse monocyte/macrophage-lineage cells. In aged skeletal muscle, dysferlin-expressing F4/80-positive macrophage-lineage cells accumulated. Finally, in a co-culture of macrophages and immature muscle cells called myoblasts, dysferlin-enriched inflammatory macrophages inhibited myogenic differentiation and myotube fusion, an effect partly mediated by soluble inflammatory factors.