Intestinal cathelicidin antimicrobial peptide shapes the gut microbiota to educate the immune system and prevent pancreatic autoimmunity

The present invention relates to the treatment of autoimmune diseases. The inventors determined that the cathelicidin related antimicrobial peptide (CRAMP) expression was defective in the colon of newborn NOD mice and that this defect was responsible for early dysbiosis. Dysbiosis stimulated the colonic epithelium to produce type I IFNs that pathologically imprinted the local immune system during the pre-weaning period. This miseducation of the immune system promoted the pancreatic autoimmune response and the development of diabetes. Increasing colonic CRAMP expression in newborn NOD mice, by local CRAMP treatment or by CRAMP-expressing probiotic, restored colonic homeostasis, and halted the diabetogenic response preventing autoimmune diabetes. Thus, they identified whether a defective colonic expression in the CRAMP antimicrobial peptide promotes autoimmunity in the pancreas. The use of CRAMP-expressing probiotic can be very helpful to treat autoimmune diseases and particularly autoimmune type 1 diabetes or obesity. Thus, the present invention relates to a recombinant CRAMP-expressing food-grade bacterium and its use in the treatment of autoimmune diseases.

Keywords: Probiotic, antimicrobial peptide, autoimmune diseases, type 1 diabete
Patent Application number: European Procedure (Patents) (EPA) - 06 Août 2021 - 21 306 102.1
Inventors:
DIANA Julien,SUN Jia
Publications:
Intestinal Cathelicidin Antimicrobial Peptide Shapes a Protective Neonatal Gut Microbiota Against Pancreatic Autoimmunity. Liang and al. Gastroenterology. 2022.

https://doi.org/10.1053/j.gastro.2021.12.272

Reference:

BIO21500-T1

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Patent filling date: 2021-08-06

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