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The anti‐inflammatory IFITM genes ameliorate colitis and partially protect from tumorigenesis by changing immunity and microbiota
Author(s) -
Alteber Zoya,
SharbiYunger Adi,
PevsnerFischer Meirav,
Blat Dan,
Roitman Lior,
Tzehoval Esther,
Elinav Eran,
Eisenbach Lea
Publication year - 2018
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12000
Subject(s) - colitis , carcinogenesis , biology , inflammation , immunology , immune system , inflammatory bowel disease , haematopoiesis , cytokine , cancer research , gene , medicine , disease , genetics , stem cell , pathology
Inflammation plays pivotal roles in different stages of tumor development. Screening for predisposing genetic abnormalities and understanding the roles these genes play in the crosstalk between immune and cancer cells will provide new targets for cancer therapy and prevention. The interferon inducible transmembrane (IFITM) genes are involved in pathogenesis of the gastro‐intestinal tract. We aimed at delineating the role of IFITM3 in colonic epithelial homeostasis, inflammation and colitis‐associated tumorigenesis using IFITM3‐deficient mice. Chemical induction of colitis in IFITM3‐deficient mice results in significantly increased clinical signs of inflammation and induction of invasive tumorigenesis. Bone marrow transplantation showed that cells of the hematopoietic system are responsible for colitis deterioration. In these mice, impaired cytokine expression skewed inflammatory response toward pathogenic Th17 with reduced expression of the anti‐inflammatory cytokine IL10 during the recovery phase. Intriguingly, mice lacking the entire IFITM locus developed spontaneous chronic colitis from the age of 14 weeks. Sequencing the 16S rRNA of naïve mice lacking IFITM3 gene, or the entire locus containing five IFITM genes, revealed these mice had significant bacterial differences from their wild‐type littermates. Our novel results provide strong evidence for the essential role of IFITM genes in ameliorating colitis and colitis‐associated tumorigenesis.