Elucidation of the role of nucleolin as a cell surface receptor for nucleic acid-based adjuvants.
Satoki KitagawaTeppei MatsudaAyaka WashizakiHirotomo MurakamiTakuya YamamotoYasuo YoshiokaPublished in: NPJ vaccines (2022)
Nucleic acid-based adjuvants such as CpG oligonucleotides (CpG ODNs) and poly(I:C) are potential vaccine adjuvants for infectious diseases and cancers. However, the mechanism by which their cell surface receptors promote their uptake into dendritic cells (DCs) and shuttle them to intracellular Toll-like receptors remains to be further investigated. Here, we demonstrated a role for nucleolin, a multifunctional DNA- and RNA-binding protein and a major constituent of the nucleolus, as one of the cell-surface receptors for nucleic acid-based adjuvants. Nucleolin on mouse DC surface bound directly to A-type CpG ODN, B-type CpG ODN, and poly(I:C) and promoted their internalization into cells following DC maturation in vitro. In human DCs, nucleolin also contributed to the binding and internalization of both types of CpG ODNs and subsequent cytokine production. Furthermore, nucleolin played a crucial role in cytokine production and activating antigen-specific antibodies and T cell responses induced by B-type CpG ODN in vivo in mice. Our findings provide valuable information that can help improve the efficacy and safety of these adjuvants.
Keyphrases
- nucleic acid
- cell surface
- dna methylation
- dendritic cells
- binding protein
- infectious diseases
- endothelial cells
- immune response
- gene expression
- signaling pathway
- induced apoptosis
- type diabetes
- risk assessment
- cell death
- mass spectrometry
- metabolic syndrome
- climate change
- regulatory t cells
- transcription factor
- cell proliferation
- single molecule
- health information
- endoplasmic reticulum stress
- insulin resistance
- high speed
- cell free
- human health