Keynote Lecture 5 “A lymphatic route for oral polysaccharide to trigger immune responses”

Many natural polysaccharides, especially those from Chinese medicines, being safe and effective, show great medicinal potential. But they are widely doubted due to their poor bioavailability. These highly polar macromolecules hardly pass through the lipophilic gut barrier and absorbed into blood. Although they have been reported to have many in vitro and in vivo bioactivities, there is a huge research gap regarding whether they can contact the target cells. Recently, the quickly increasing studies on gut microbiota indicated that these carbohydrates may work as carbon source for gut microbiota to produce short-chain fatty-acids that are associated with many beneficial effects. However, most of these studies finally focused on butyrate, which is weak to explain the diverse bioactivities of these so many different polymers. Radix Astragali Polysaccharide (RAP) is a good example, which has been reported to have many in vitro and in vivo immune- related bioactivities such as activating innate immune cells, anti-cancer, anti-viral, and immunomodulatory properties. Our previous study found that RAP quickly induced immune response in the intestinal Peyer’s patches 2 hours after oral dosing, which happened before RAP arriving cecum where RAP will be degraded into SCFAs by gut microbiota. There must be another way for RAP to contact immune cells. Our further investigation revealed that RAP, remaining intact polymer, was quickly transported by M -cell into Peyer's patches where it directly targeted follicle dendritic cells and initiated antitumor immune responses. RAP was even transported by DCs to protect chemotherapy-suppressed bone marrow cells and hematopoietic stem cells (HSC) in vivo and in vitro. This route was already verified to apply to human subjects. These findings refreshed people’s knowledge regarding polysaccharide’s oral bioavailability. This new absorption route eliminates the above research gap and provides new ideas for finding lymphatic-targeted new drug preparation. More importantly, RAP showed its great potential to work as the special carrier in a lymphatic- targeting drug delivery system. Especially, RAP may be a promising dual-function adjuvant for oral vaccine: immune-stimulator and lymphatic-targeting antigen carrier ([Fig. 1]).

Fig 1 RAP entered PPs via M-cell transcytosis and directly contacted DCs to trigger immune response after oral dosing.

 

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Conflict of Interest

The authors declare no conflict of interest.

Publikationsverlauf

Artikel online veröffentlicht:
16. November 2023