The immune regulatory effects of tetrahedral framework nucleic acid on human T cells via the mitogen-activated protein kinase pathway

Objectives Autoimmune diseases are a heterogeneous group of diseases which lose the immunological tolerance to self-antigens. It is well recognized that irregularly provoked T cells participate in the pathological immune responses. As a novel nanomaterial with promising applications, tetrahedral framework nucleic acid (TFNA) nanostructure was found to have immune regulatory effects on T cells in this study. Materials and Methods To verify the successful fabrication of TFNA, the morphology of TFNA was observed by atomic force microscopy (AFM) and dynamic light scattering. The regulatory effect of TFNA was evaluated by flow cytometry after cocultured with CD3+ T cells isolated from healthy donors. Moreover, the associated signaling pathways were investigated. Finally, we verified our results on the T cells from patients with neuromyelitis optica spectrum disorder (NMOSD), which is a typical autoimmune disease induced by T cells. Results We revealed the alternative regulatory functions of TFNA in human primary T cells with steady status via the JNK signaling pathway. Moreover, by inhibiting both JNK and ERK phosphorylation, TFNA exhibited significant suppressive effects on IFN gamma secretion from provoking T cells without affecting TNF secretion. Similar immune regulatory effects of TFNA were also observed in autoreactive T cells from patients with NMOSD. Conclusions Overall, our results revealed a potential application of TFNA in regulating the adaptive immune system, as well as shed a light on the treatment of T cell-mediated autoimmune diseases.

Automated summary

The study demonstrated the immunomodulatory effects of TFNA nanostructure on T cells, showing significant suppressive effects on IFN gamma secretion in provoking T cells through the JNK signaling pathway in primary human T cells. Similar immune regulatory effects were also observed in autoreactive T cells from patients with NMOSD. These findings suggest the potential application of TFNA in regulating the adaptive immune system and treating T cell-mediated autoimmune diseases.