Associations Between Th17 Cell Markers (IL-23R, CCR6, and IL-17) and Clinical Profiles in Sjögren's Disease.

Background/objectives: Sjögren's disease (SjD) is an autoimmune disorder characterized by lymphocytic infiltration and inflammation leading to exocrine gland dysfunction. Th17 cells play a central role in autoimmune pathology and are defined by markers such as IL-23R, CCR6, and IL-17. However, the combined characterization of these markers and their relevance in SjD remain poorly understood. Methods: Forty-one participants were enrolled, including twenty-two patients with SjD and nineteen control subjects (CS). Peripheral blood immunophenotyping was performed using multicolor flow cytometry, and serum cytokine concentrations were quantified within a multiplex assay. Non-parametric analyses were conducted using the Mann-Whitney U test and Spearman's rank correlation. Results: Compared with CS, patients with SjD exhibited higher frequencies of CD3(+)CD4(+)IL-23R(+) T cells and elevated IL-23 levels. The proportion of CCR6(+)IL-23R(+) T helper cells tended to be higher in SjD than in controls, although this difference did not reach statistical significance (8.8% vs. 5.3%, p = 0.056). Within clinical subgroups, anti-Ro-negative patients showed increased frequencies of CD3(+)CD4(+)IL-23R(+) cells. Patients with hypertriglyceridemia displayed reduced frequencies of CCR6(+)IL-23R(+)IFN-γ(+) cells, whereas normal HDL levels were associated with CCR6 expression and IL-17A production. Conclusions: These findings highlight the heterogeneity of Th17 cells in Sjögren's disease and reinforce the involvement of the IL-23/IL-23R axis in disease pathogenesis. Exploratory associations between Th17 subsets and lipid parameters suggest a potential immunometabolic interplay that warrants further investigation. Together, these data provide a more comprehensive view of Th17 dynamics in SjD and establish a foundation for future mechanistic studies in larger cohorts and tissue-specific contexts.