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Microbial therapeutics for acute colitis based on genetically modified Lactococcus lactis hypersecreting IL-1Ra in mice

Experimental & Molecular Medicine 2020년 52권 9호 p.25 ~ 25
Namai Fu, Shigemori Suguru, Ogita Tasuku, Sato Takashi, Shimosato Takeshi,
소속 상세정보
 ( Namai Fu ) - Shinshu University Institute for Biomedical Sciences Department of Biomolecular Innovation
 ( Shigemori Suguru ) - Shinshu University Institute for Biomedical Sciences Department of Biomolecular Innovation
 ( Ogita Tasuku ) - Shinshu University Institute for Biomedical Sciences Department of Biomolecular Innovation
 ( Sato Takashi ) - Shinshu University Institute for Biomedical Sciences Department of Biomolecular Innovation
 ( Shimosato Takeshi ) - Shinshu University Institute for Biomedical Sciences Department of Biomolecular Innovation

Abstract


The increased incidence of inflammatory bowel disease (IBD) in Western and rapidly Westernizing developing countries poses a global pandemic threat. The development of affordable drugs for treating IBD worldwide is thus a priority. Genetically modified lactic acid bacteria (gmLAB) as microbial therapeutics are inexpensive protein producers suitable for use as carriers of protein to the intestinal mucosa. Here, we successfully constructed gmLAB hypersecreting interleukin 1 receptor antagonist (IL-1Ra). Oral administration of these gmLAB suppressed body weight reduction and exacerbation of the disease activity index score in mice with acute colitis and decreased the number of CD4+ IL-17A+ cells in the mesenteric lymph nodes. These data suggest that the gmLAB deliver IL-1Ra to the colon, where it inhibits IL-1 signaling. We thus developed a novel IBD therapeutic that blocks IL-1 signaling using a gmLAB protein delivery system. This system could be an inexpensive oral microbial therapeutic.

키워드

Immunology; Protein delivery

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