Lactobacillus delivery of bioactive interleukin-22

Microb Cell Fact. 2017 Aug 23;16(1):148. doi: 10.1186/s12934-017-0762-1.

Abstract

Background: Interleukin-22 (IL-22) plays a prominent role in epithelial regeneration and dampening of chronic inflammatory responses by protecting intestinal stem cells from immune-mediated tissue damage. IL-22 has a considerable therapeutic potential in graft-versus-host disease (GVHD), which is a frequent and challenging complication following allogeneic stem cell transplantation. The aim of our study was to engineer Lactobacillus for delivery of IL-22 directly to the intestinal mucosa as a new therapeutic strategy for GVHD.

Results: The secretion and surface anchoring of mouse IL-22 by Lactobacillus paracasei BL23 was demonstrated by Western blot and flow cytometry. Both secreted and anchored mouse IL-22 produced by Lactobacillus was biologically active, as determined by its ability to induce IL-10 secretion in the Colo 205 human colon cancer cell line.

Conclusions: We have demonstrated the secretion and surface anchoring of bioactive IL-22 by Lactobacillus. Our results suggest that IL-22 expressing lactobacilli may potentially be a useful mucosal therapeutic agent for the treatment of GVHD, provided that chromosomal integration of the IL-22 expression cassettes can be achieved.

Keywords: GVHD; Lactobacillus paracasei BL23; Mouse interleukin-22.

MeSH terms

  • Animals
  • Cell Line
  • Flow Cytometry
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / therapy
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-22
  • Interleukins / genetics
  • Interleukins / immunology*
  • Interleukins / metabolism*
  • Interleukins / pharmacology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Lacticaseibacillus paracasei / genetics*
  • Lacticaseibacillus paracasei / metabolism*
  • Mice
  • Plasmids
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • Interleukins
  • Recombinant Proteins
  • Interleukin-10