Oral Delivery of IL-27 Recombinant Bacteria Attenuates Immune Colitis in Mice

Miranda L. Hanson, Julie A. Hixon, Wenqing Li, Barbara K. Felber, Miriam R. Anver, C. Andrew Stewart, Brian M. Janelsins, Sandip K. Datta, Wei Shen, Mairi H. McLean, Scott K. Durum*

*Corresponding author for this work

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

BACKGROUND & AIMS: Treatment of inflammatory bowel disease would benefit from specific targeting of therapeutics to the intestine. We developed a strategy for localized delivery of the immunosuppressive cytokine interleukin (IL)-27, which is synthesized actively in situ by the food-grade bacterium Lactococcus lactis (LL-IL-27), and tested its ability to reduce colitis in mice.

METHODS: The 2 genes encoding mouse IL-27 were synthesized with optimal codon use for L lactis and joined with a linker; a signal sequence was added to allow for product secretion. The construct was introduced into L lactis. Colitis was induced via transfer of CD4(+)CD45RB(hi) T cells into Rag(-/-) mice to induce colitis; 7.5 weeks later, LL-IL-27 was administered to mice via gavage. Intestinal tissues were collected and analyzed. 

RESULTS: LL-IL-27 administration protected mice from T-cell transfer-induced enterocolitis and death. LL-IL-27 reduced disease activity scores, pathology features of large and small bowel, and levels of inflammatory cytokines in colonic tissue. LL-IL-27 also reduced the numbers of CD4(+) and IL-17(+) T cells in gut-associated lymphoid tissue. The effects of LL-IL-27 required production of IL-10 by the transferred T cells. LL-IL-27 was more effective than either LL-IL-10 or systemic administration of recombinant IL-27 in reducing colitis in mice. LL-IL-27 also reduced colitis in mice after administration of dextran sodium sulfate. 

CONCLUSIONS: LL-IL-27 reduces colitis in mice by increasing the production of IL-10. Mucosal delivery of LL-IL-27 could be a more effective and safer therapy for inflammatory bowel disease.

Original languageEnglish
Pages (from-to)210-221.e13
Number of pages25
JournalGastroenterology
Volume146
Issue number1
Early online date9 Oct 2013
DOIs
Publication statusPublished - Jan 2014

Keywords

  • Mouse Model
  • Crohn's Disease
  • Ulcerative Colitis
  • Immune Regulation

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