Analysis of CCR9, CXCR5 and ICOS in Circulating Follicular Helper T Cell-like Populations in Sjögren’s Disease

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.