Update on the Aetiopathogenesis of Sjögren Disease: From Interferon Signaling to Epithelial Dysfunction

Sjögren disease (SjD) is a prototypical autoimmune disease whose management has long suffered from a limited understanding of its underlying pathophysiological mechanisms. However, major advances have been made over the past decade. The innate immune system is now recognized as playing a key role in the early stages of the disease, particularly through activation of interferon (IFN) pathways, driven in part by epithelial cells, which actively attract autoreactive lymphocytes. Furthermore, the mechanisms of B-cell activation in SjD are now better understood, notably with the recognition of BAFF (B-cell activating factor), a Tumor necrosis factor (TNF) family cytokine, whose production is highly dependent on type I and II IFN signaling. The involvement of other cell types, such as fibroblasts and T cells, has also been underlined. Significant progress has been achieved in elucidating lymphomagenesis, the most severe complication of SjD. Together, these advances provide a clearer picture of SjD pathogenesis and open avenues for the development of new targeted therapeutic strategies.