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

TL;DR

This paper reviews recent discoveries about the causes of Sjögren disease, focusing on immune system pathways and potential new treatments.

Contribution

The paper highlights new insights into interferon signaling, B-cell activation, and epithelial dysfunction in Sjögren disease pathogenesis.

Findings

Interferon pathways and epithelial cells play a key role in attracting autoreactive lymphocytes in early Sjögren disease.

BAFF, a TNF family cytokine, is crucial for B-cell activation and is regulated by interferon signaling.

Progress in understanding lymphomagenesis offers new therapeutic strategies for Sjögren disease.

Abstract

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.

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