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

Abstract

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 IFNγ 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.

Tetrahedral Framework Nuclear Acids Can Regulate Interleukin-17 Pathway to Alleviate Inflammation and Inhibit Heterotopic Ossification in Ankylosing Spondylitis

“…Due to the source of its components, tFNAs are highly programmable and easy to modify and label with very low immunogenicity. Recently, studies have found that tFNAs can penetrate different cells to affect their various biological activities. − Moreover, our previous research has found that tFNAs or its derivatives could inhibit inflammation via regulating the IL-17 pathway. , Li and his colleagues discovered that tFNAs loaded with resveratrol could suppress inflammation and ameliorate insulin resistance via inhibiting Th1 and Th17 cell activation to reduce the production of IL-17 . In our study, tFNAs were used as a treatment option for AS, and significant therapeutic effects were observed both in vivo and in vitro .…”

“…Tetrahedral frame nucleic acids (tFNAs) are bioactive nanomaterial with tetrahedron-like structures that have been widely studied in the biomedical field. − Its editability allows it to carry coding sequence in a framework structure for the treatment of specific diseases. The small size and the negative surface potential of tFNAs determine that it could be quickly ingested by cells to exert various biological effects.…”

“…28−41 Moreover, our previous research has found that tFNAs or its derivatives could inhibit inflammation via regulating the IL-17 pathway. 42,43 Li and his colleagues discovered that tFNAs loaded with resveratrol could suppress inflammation and ameliorate insulin resistance via inhibiting Th1 and Th17 cell activation to reduce the production of IL-17. 39 In our study, tFNAs were used as a treatment option for AS, and significant therapeutic effects were observed both in vivo and in vitro.…”

Homotypic targeting of immunomodulatory nanoparticles for enhanced peripheral and central immunity

“… 5 , 10 , 11 However, free CpG ODNs are susceptible to nuclease cleavage and have poor cell permeability due to their anionic and hydrophilic properties. 12 , 13 , 14 , 15 , 16 Although phosphorothioate modification of the backbone can confer the resistance to nuclease degradation, it concurrently increases the cytotoxicity and thereby limits the clinical utilization of CpG ODNs. 17 , 18 , 19 , 20 Therefore, it is highly appealing to develop efficient and safe delivering strategies for CpG ODNs, improving their bioavailability and biocompatibility.…”