Secretory IgA (SIgA), the predominant class of antibody in intestinal secretions, serves as the first line of defense against enteric infections. SIgA has also been proposed to function in immune surveillance, given that both SIgA and SIgA-antigen complexes are actively transported by Peyer’s patch M cells from the intestinal lumen to sub-epithelial dendritic cells (DCs). DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN) is a kind of SIgA receptor, and their interaction reveals a mechanism by which DCs could collaborate with M cells in immune surveillance at mucosal surfaces. Moreover, SIgA also has a powerful anti-inflammatory effect due to its ability to interact with DC through the specific intercellular adhesion molecule grabbing DC-SIGN. Therefore, there are huge application potentials in the research of DC-SIGN aimed at novel anti-infective drugs while Creative Biolabs pays more attention in related areas. Based on skilled employees and established platforms, we gained remarkable achievements and we are glad to share our experience with partners all over the world.
Introduction of DC-SIGN Receptor
DCs are a heterogeneous population and the most potent antigen-presenting cells known so far which are responsible for generating strong Ag-specific immune responses, as well as for inducing tolerance and maintenance of immune homeostasis. DC-SIGN is a type II transmembrane lectin receptor and has increased greatly in recent years due to important discoveries documenting its immune-related functions. DC-SIGN contains a carbohydrate recognition domain (CRD), a neck region composed of 7 and a half repeats containing 23 amino acid residue repeats, and a transmembrane region followed by a cytoplasmic tail containing recycling and internalization motifs. The expression of DC-SIGN is most attractive due to its specificity between different DCs. DC-SIGN is abundantly expressed on immature DCs which suggests that DC-SIGN contributes to the differentiation and maturation of DCs.
Fig.1 Schematic structure of DC-SIGN and amino-acid sequence alignment of the neck-repeat domain. (Svajger, 2010)
Function of DC-SIGN Receptor
The involvement of DC-SIGN in various DC functions including differentiation, migration, antigen capture, and T cell priming. Moreover, DCs have evolved unique ways in which they regulate immunity and contribute to tolerance induction. DC-SIGN is implicated in the immunoregulation of DCs while DC-SIGN has emerged as a key player in the induction of immune responses by modulating Toll-like receptor-induced activation of DCs. However, DC-SIGN also provides an approach to escape immune surveillance, while HIV-1 is a perfect example of a virus that exploits native DC-SIGN functions for infection.
Fig.2 HIV-1 interaction with DC-SIGN and subsequent events. (Svajger, 2010)
IgA-DC-SIGN Interaction
The interaction between DC-SIGN and SIgA was demonstrated by a series of experiments as selectively binding activity, while this interaction was Ca2+-dependent, and could be inhibited by the addition of mannan. Such data suggest that DC-SIGN functions contain recognition and internalization of SIgA and SIgA-antigen complexes by mucosal DCs, which indicates DC-SIGN-mediated uptake of SIgA-antigen complexes by DCs could serve as an immune surveillance mechanism important in the maintenance of mucosal immunity and intestinal homeostasis.
Fig.3 Co-localization of SIgA and DC-SIGN on the surfaces of THP-1 cells. (Baumann, 2010)
Although many questions about the IgA-DC-SIGN interaction mechanism and significance remain, it is no doubt that DC-SIGN occupies an important position in the immune response. Creative Biolabs is glad to be the help of your scientific research based on our skilled groups and rich experience. Please feel free to contact us for more details.
References
- Svajger, U.; et al. C-type lectin DC-SIGN: an adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity. Cellular signalling. 2010, 22(10), 1397-1405.
- Baumann, J.; et al. Recognition of secretory IgA by DC-SIGN: implications for immune surveillance in the intestine. Immunology letters. 2010, 131(1), 59-66.
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