Th118 - T Follicular Helper 1 Cells in Blood Potentially Mirror Salivary Gland-infiltrating T Cells in Sjögren’s Disease

Abstract Text: Sjögren’s disease (SjD) is characterized by inflammation within the labial salivary glands (LSG) and systemic autoimmunity. However, the mechanisms linking blood and tissue immune responses remain poorly defined. In this study, we examined the immunological profile of circulating CD4+ T cell subsets in SjD, focusing on Tfh1 cells that resemble LSG-infiltrating cells. Using multicolor flow cytometry, we found that CXCR3+CXCR5+ Tfh1 cells were significantly elevated in SjD than in healthy controls, both in circulation and in the LSG, with PD-1+ICOS+ Tfh1 cells correlating positively with antinuclear and anti-SS-A/B antibody titers. Conversely, while CXCR3+CXCR5- Th1 cells were increased in the LSG, their frequency was diminished in circulation. TCR sequencing revealed notable T cell repertoire overlap between circulating Tfh1 cells and LSG T cells, with high similarities. Further analysis of the LSG microenvironment in SjD patients showed upregulation of IL-6, IL-12, IL-21, and TGF-β. Specifically, TGF-β in conjunction with TCR stimulation, promoted Tfh1 cell differentiation, driving IL-2, TNF-α, and IL-21 production and facilitating differentiation toward CD19+CD38+ B cells. Our findings suggest that Tfh1 cells in circulation may mirror the inflammatory and autoimmune activity in the LSG of SjD patients, with TGF-β playing a central role in driving disease-related Tfh1 cell differentiation. This study underscores the potential of Tfh1 cells as biomarkers and therapeutic targets in SjD, warranting further investigation.