Superior low-immunogenicity of tilapia type I collagen based on unique secondary structure with single calcium binding motif over terrestrial mammals by inhibiting activation of DC intracellular Ca 2+ -mediated STIM1-Orai1/NF-кB pathway

The reason for low- or non-immunogenicity of fish collagens is still in doubt, which, to some extent, bottlenecks their production and clinical application as biomaterials. Employing bovine or porcine type I collagens (BCI or PCI) as controls in this paper, we intensively investigate the influence of tilapia type I collagens (TCI) on the function of dendritic cells (DCs) and T cells. From bio-informatic analyses, as well as data obtained in vitro and in vivo, we find the variations in amino acid sequences lead to only one calcium binding motif in the secondary structure of TCI, compared with three in BCI or PCI. So when TCI (together with the minor amount of Ca 2+ they take) are uptaken, intracellular [Ca 2+ ] remains stable and DCs maintain immature. On the contrary, those that have uptaken PCI or BCI experience not only increased [Ca 2+ ] in the plasma but also phosphorylation of p65, resulting in activation of STIM1-Orai1/NF-кB signaling pathway and DC maturation. We fully prove our results on mice models, with no obvious cellular and humoral immune reactions. Our study primarily reveal the underlying mechanisms why TCI, different from BCI or PCI, show almost non-immunogenicity. Our findings are of great importance for the promotion and wide application of TCI in biomedicine.