Collectively, these data suggest that an important function of exosomes in healthy skin is to dampen proinflammatory IFN signaling in keratinocytes, thus contributing to homeostasis, and that the lack of this anti‐inflammatory effect of exosomes secreted by SSc fibroblasts on keratinocytes may lead to loss of homeostasis and contribute to a more proinflammatory state in patients with SSc. This evidence concerns the gene IFNA1 and systemic sclerosis.