Tetrahedral Framework Nucleic Acids Reestablish Immune Tolerance and Restore Saliva Secretion in a Sjögren’s Syndrome Mouse Model

As one of the most frequent autoimmune diseases, Sjogren's syndrome (SS) is characterized by overactive lymphocytic infiltration in the exocrine glands, with ensuing dry mouth and dry eyes. Unfortunately, so far, there are no appropriate therapies without causing overall immunosuppression. Tetrahedral framework nucleic acids (tFNAs) were regarded as promising nanoscale materials whose immunomodulatory capabilities have already been verified. Herein, we reveal, for the first time, that tFNAs were utilized to treat SS in female nonobese diabetic (NOD) mice, the animal model used for SS. We proved a 250 nM tFNA treatment was successful in suppressing inflammation and stimulating saliva secretion in NOD mice. Specialised proteins for the secretory function and structure of acinar cells in submandibular glands (SMGs) were restored. It has been the permanent goal for SS treatment to establish immune tolerance and stop disease development. Surprisingly, tFNA treatment guided T cells toward regulatory T cells (Tregs), while suppressing T helper (Th) cell responses. Th cells include Th1, Th17, and follicular helper T (Tfh) cells. Tregs are highly significant in immune tolerance. Inducing Tregs is a promising approach to reestablish immune tolerance. Comparable results were also observed in B cell responses. Reductions in the percentage of germinal center (GC) B cells and plasma cells were detected, and a marked increase in the percentage of regulatory B cells (Bregs) was also noticed. The mechanisms of inducing Tregs may associated with cytokine changes. Changes of T cell subsets, especially changes of Tfh, may influence the differentiation of B cells accordingly. Collectively, our results demonstrated the immunomodulatory capacities of tFNAs once again, which may provide a novel, safe, and effective option for the treatment of SS and other autoimmune diseases.