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2022-ACS Biomat Sci Eng - Chua et al. .pdf (3.5 MB)

An Engineered Probiotic Produces a Type III Interferon IFNL1 and Reduces Inflammations in in vitro Inflammatory Bowel Disease Models

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posted on 2023-09-22, 08:12 authored by Koon Jiew Chua, Hua Ling, In Young HwangIn Young Hwang, Hui Ling Lee, John C. March, Yung Seng LeeYung Seng Lee, Matthew Wook Chang

The etiology of inflammatory bowel diseases (IBDs) frequently results in the uncontrolled inflammation of intestinal epithelial linings and the local environment. Here, we hypothesized that interferon-driven immunomodulation could promote anti-inflammatory effects. To test this hypothesis, we engineered probiotic Escherichia coli Nissle 1917 (EcN) to produce and secrete a type III interferon, interferon lambda 1 (IFNL1), in response to nitric oxide (NO), a well-known colorectal inflammation marker. We then validated the anti-inflammatory effects of the engineered EcN strains in two in vitro models: a Caco-2/Jurkat T cell coculture model and a scaffold-based 3D coculture IBD model that comprises intestinal epithelial cells, myofibroblasts, and T cells. The IFNL1-expressing EcN strains pregulated Foxp3 expression in T cells and thereafter reduced the production of pro-inflammatory cytokines such as IL-13 and -33, significantly ameliorating inflammation. The engineered strains also rescued the integrity of the inflamed epithelial cell monolayer, protecting epithelial barrier integrity even under inflammation. In the 3D coculture model, IFNL1-expressing EcN treatment enhanced the population of regulatory T cells and increased anti-inflammatory cytokine IL-10. Taken together, our study showed the anti-inflammatory effects of IFNL1-expressing probiotics in two in vitro IBD models, demonstrating their potential as live biotherapeutics for IBD immunotherapy.

History

Journal/Conference/Book title

ACS Biomaterials Science & Engineering

Publication date

2022-11-18

Version

  • Published

Corresponding author

Matthew Wook Chang

Project ID

  • 14866 (R-NRF-A401-0001) Fighting Amebiasis with bacteria: a combined approach with natural probiotics and engineered bacteria

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