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 (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    146 Citations (Scopus)
    87 Downloads (Pure)

    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+CD45RBhi 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 date11 Oct 2013
    DOIs
    Publication statusPublished - 1 Jan 2014

    Keywords

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

    ASJC Scopus subject areas

    • Hepatology
    • Gastroenterology

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