Jefte Felipe Uribe-Martínez

Circulant follicular helper T cells (cTfh) are a specialized subset of CD4⁺ T cells that induce immunoglobulin class switching and antibody secretion in plasma cells through the production of IL-21. To investigate the role of cTfh-like cells in the development of Sjögren’s disease (SjD), we analyzed the circulating Tfh-like cells, their production of IL-21 and IL-4, and the co-expression of ICOS, CXCR5, and CCR9 by flow cytometry, and evaluated their association with clinical characteristics of the disease. Percentages of CD4⁺ IL-21⁺ CXCR5⁺ ICOS⁺ CCR9⁺ IL-4⁺ T cells were analyzed in peripheral blood samples from 20 healthy controls (HCs) and 19 patients with SjD. Serum levels of IL-1β, IL-4, IL-6, IL-21, and sCD40L were assessed using a Luminex assay. Laboratory data included anti-Ro/La antibodies, immunoglobulin levels (IgA and IgG), focus score, disease duration, and ESDDAI/SSDDI scores. Decreased frequencies of CXCR5⁺ IL-21⁺ T cells and CCR9⁺ IL-4⁺ T cells were observed in the peripheral blood of patients with SjD. Heatmap analysis was used to identify correlations between cTfh-like cells and clinical parameters. Elevated proportions of cTfh-like cells were positively correlated with disease severity, inflammatory markers, and autoantibody production. High-dimensional analysis identified distinct subpopulations with differential expression of ICOS, CXCR5, CCR9 and IL-21, suggesting heterogeneity of these cells in SjD and their involvement in disease pathogenesis.

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.