Decoding the IL-12 Cytokine Family in Sjögren's Disease: Pathogenic Networks and Translational Implications

Sjögren's disease (SjD) is a systemic autoimmune disorder characterized by exocrine-gland dysfunction and heterogeneous extraglandular manifestations. The IL-12 cytokine family, comprising IL-12, IL-23, IL-27, and IL-35, may contribute to SjD through interconnected immune and JAK-STAT signaling pathways.

To review the roles of IL-12-family cytokines in SjD pathogenesis and identify current knowledge gaps and translational challenges.Methods: A narrative literature search was conducted using PubMed/MEDLINE, Scopus, and Web of Science. Keywords and combinations related to SjD, IL-12, IL-23, IL-27, IL-35, cytokine signaling, JAK-STAT pathways, and immune responses were used to identify relevant studies. Human and experimental studies addressing the biological or pathological roles of IL-12-family cytokines in SjD were considered, and reference lists of relevant publications were additionally screened.

IL-12 promotes STAT4-dependent Th1 differentiation and IFN-γ production, whereas IL-23 supports pathogenic Th17 responses. IL-27 exhibits context-dependent regulatory or proinflammatory effects, while IL-35 is generally associated with immunoregulatory activity, although human findings remain inconsistent.

IL-12-family cytokines may function as an interconnected network in SjD rather than independently. Further longitudinal and tissue-specific studies are needed to validate their potential for patient stratification and therapeutic targeting.