Nitrate Prevents Sjögren's Disease by Modulating T Helper Cells via NF-κB Pathway Suppression.

Abstract

Objective: Sjögren's disease (SjD) is a chronic autoimmune disease characterized by abnormal T helper (Th) cell distribution in the salivary glands (SGs). Although nitrate can regulate immune responses and preserve SGs function, its preventive effects on SjD remain unexplored.

Methods: Nonobese diabetic (NOD)/Ltj mice were used as a secondary Sjögren's disease (sSjD) animal model. From 6 to 16 weeks of age, the mice received either sodium nitrate (2 mM) in drinking water (SjD + Nit group) or sodium chloride (SjD + NaCl group). Salivary flow rates were recorded biweekly, and submandibular glands were collected at 16 weeks for histological analysis. Th subsets ratios were determined using flow cytometry, and mRNA sequencing was used to explore nitrate's preventive mechanism.

Results: Nitrate pretreatment preserved salivary function and reduced lymphocyte infiltration. T cell related genes were downregulated, while salivary function genes were upregulated. Differentiation pathways for Th cell subsets were downregulated in the SjD + Nit group, and nitrate modulated the abnormal balance of Th cells, regulatory T cells (Tregs) in the SGs, and peripheral blood, suppressing the NF-κb pathway of sSjD.

Conclusions: Preventive nitrate administration may preserve SG function, rebalance Th cells, and suppress NF-κB pathway, offering a potential treatment for SjD.