Lactobacillus delivery of bioactive interleukin-22

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Interleukin-22 (IL-22) is crucial for epithelial repair and reducing chronic inflammation, protecting intestinal stem cells.
• Graft-versus-host disease (GVHD) is a significant complication of allogeneic stem cell transplantation, necessitating novel therapeutic strategies.
• IL-22 shows promise for treating GVHD due to its protective effects on intestinal tissues.

Purpose of the Study:

• To engineer Lactobacillus bacteria for the mucosal delivery of IL-22.
• To develop a novel therapeutic approach for GVHD using genetically modified probiotics.
• To investigate the potential of Lactobacillus as a vehicle for delivering therapeutic proteins to the gut.

Main Methods:

• Genetic engineering of Lactobacillus paracasei BL23 to express mouse IL-22.
• Confirmation of IL-22 secretion and surface anchoring using Western blot and flow cytometry.
• Assessment of the biological activity of produced IL-22 by measuring IL-10 induction in colon cancer cells.

Main Results:

• Successful secretion and surface anchoring of mouse IL-22 by Lactobacillus paracasei BL23 were confirmed.
• The IL-22 produced by the engineered Lactobacillus was biologically active.
• The active IL-22 induced IL-10 secretion in the Colo 205 human colon cancer cell line, demonstrating its functional capacity.

Conclusions:

• Lactobacillus can be engineered to secrete and anchor bioactive IL-22.
• IL-22-expressing lactobacilli represent a potential mucosal therapeutic agent for GVHD.
• Further research focusing on chromosomal integration of IL-22 expression cassettes is needed for clinical application.