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

Cell Prolif. 2021 Aug;54(8):e13084. doi: 10.1111/cpr.13084. Epub 2021 Jun 25.

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.

Keywords: T cells; autoimmunity; immune regulatory; neuromyelitis optica spectrum disorder; tetrahedral framework nucleic acid.

MeSH terms

  • Adult
  • Cells, Cultured
  • Cyclosporine / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism*
  • Nanostructures / chemistry
  • Neuromyelitis Optica / metabolism
  • Neuromyelitis Optica / pathology
  • Nucleic Acids / chemical synthesis
  • Nucleic Acids / chemistry
  • Nucleic Acids / pharmacology*
  • Phosphorylation / drug effects
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • Nucleic Acids
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Cyclosporine
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases