Sjögren’s disease (SjD) is a chronic autoimmune disease characterized by lymphocytic infiltration and progressive dysfunction of the exocrine glands, which may eventually result in multi-organ and multisystem involvement, and substantially impairs patients’ quality of life and survival. Previous studies demonstrate that the JAK family, including tyrosine kinase 2 (TYK2), and its downstream signaling pathways are involved in immune cell activation, migration, and epithelial injury. This study aimed to investigate TYK2 expression in peripheral blood mononuclear cells (PBMCs) from patients with Sjögren’s disease and to preliminarily evaluate its potential as a therapeutic target.

A total of 46 patients with SjD were enrolled according to the 2016 ACR/EULAR classification criteria. PBMCs were isolated from peripheral blood, and relative TYK2 mRNA expression was measured by RT-qPCR. Clinical indicators were collected, and disease activity was assessed with the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI). In addition, PBMCs from 8 patients were collected and cultured in vitro for 48 hours with either 5 μmol/L deucravacitinib, a TYK2 inhibitor, or an equal volume of solvent as a control, then compared the proportions of immune cell subsets between the two groups.

Compared with the remission group (ESSDAI < 5), TYK2 expression (2^-ΔΔCt) significantly increased in the active disease group (ESSDAI ≥ 5). And similar results were observed when patients were grouped with ClinESSDAI (Figure 1). Patients with glandular involvement also showed significantly higher TYK2 expression (3.281 vs. 1.523, P = 0.013). Correlation analysis demonstrated that TYK2 expression was negatively correlated with platelet count (β = -0.249, P = 0.045). In vitro experiments showed that TYK2 inhibition reduced the proportions of follicular helper T (Tfh) cells, Th1 cells, and B cells in PBMCs from patients with SjD, while the proportion of B10 cells showed an increasing trend (Figure 2).

TYK2 expression in PBMCs was associated with disease activity in Sjögren’s disease and was negatively correlated with platelet count, suggesting that TYK2 may be involved in disease progression and hematologic manifestations in SjD. In vitro, inhibition of TYK2 can reduce the proportions of Tfh, Th1, and B cells while increasing the proportion of B10 cells, supporting the potential immunomodulatory role of TYK2 as a therapeutic target in SjD.