Elucidation of the role of nucleolin as a cell surface receptor for nucleic acid-based adjuvants

Autor: Satoki Kitagawa, Teppei Matsuda, Ayaka Washizaki, Hirotomo Murakami, Takuya Yamamoto, Yasuo Yoshioka
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: npj Vaccines, Vol 7, Iss 1, Pp 1-15 (2022)
Druh dokumentu: article
ISSN: 2059-0105
DOI: 10.1038/s41541-022-00541-6
Popis: Abstract 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.
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