Human Umbilical Cord Mesenchymal Stem Cell-derived Exosome Regulates Intestinal Type 2 Immunity

Abstract

Aims: The aim of this study was to investigate the role of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exo) in regulating the intestinal type 2 immune response for either protection or therapy. Background: hUCMSC-Exo was considered a novel cell-free therapeutic product that shows promise in the treatment of various diseases. Type 2 immunity is a protective immune response classified as T-helper type 2 (Th2) cells and is associated with helminthic infections and allergic diseases. The effect of hUCMSC-Exo on intestinal type 2 immune response is not clear. Method: C57BL/6 mice were used to establish intestinal type 2 immune response by administering of H.poly and treated with hUCMSC-Exo before or after H.poly infection. Intestinal organoids were isolated and co-cultured with IL-4 and hUCMSC-Exo. Then, we monitored the influence of hUCMSC-Exo on type 2 immune response by checking adult worms, the hyperplasia of tuft and goblet cells. Result: hUCMSC-Exo significantly delays the colonization of H.poly in subserosal layer of duodenum on day 7 post-infection and promotes the hyperplasia of tuft cells and goblet cells on day 14 post-infection. HUCMSC-Exo enhances the expansion of tuft cells in IL-4 treated intestinal organoids, and promotes lytic cell death. result: Our experimental results revealed that hUCMSC-Exo significantly delays the colonization of H.poly in subserosal layer of duodenum on day 7 post infection, but promotes the hyperplasia of tuft cells and goblet cells on day 14 post infection, and hUCMSC-Exo enhances the expansion of tuft cells in IL-4 treated intestinal organoids, and promotes lytic cell death. Conclusion: Our study demonstrates hUCMSC-Exo may benefit the host by increasing the tolerance at an early infection stage and then enhancing the intestinal type 2 immune response to impede the helminth during Th2 priming. Our results show hUCMSC-Exo may be a positive regulator of type 2 immune response, suggesting hUCMSC-Exo has a potential therapeutic effect on allergic diseases.