Open AccessIrgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation
Author(s) -
Bo Liu,
Ajay Gulati,
Viviana Cantillana,
Stanley C. Henry,
Elyse A. Schmidt,
Xiaoju Daniell,
Emily Grossniklaus,
Alexi A. Schoenborn,
R. Balfour Sartor,
Gregory A. Taylor
Publication year - 2013
Publication title -
american journal of physiology. gastrointestinal and liver physiology/american journal of physiology: gastrointestinal and liver physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.644
H-Index - 169
eISSN - 1522-1547
pISSN - 0193-1857
DOI - 10.1152/ajpgi.00071.2013
Subject(s) - autophagy , inflammation , microbiology and biotechnology , biology , paneth cell , immune system , intestinal permeability , mitophagy , immunology , small intestine , biochemistry , apoptosis
Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase (IRG) M (IRGM). IRGs comprise a family of proteins known to confer resistance to intracellular infections through various mechanisms, including regulation of phagosome processing, cell motility, and autophagy. However, despite its association with CD, the role of IRGM and other IRGs in regulating intestinal inflammation is unclear. We investigated the involvement of Irgm1, an ortholog of IRGM, in the genesis of murine intestinal inflammation. After dextran sodium sulfate exposure, Irgm1-deficient [Irgm1 knockout (KO)] mice showed increased acute inflammation in the colon and ileum, with worsened clinical responses. Marked alterations of Paneth cell location and granule morphology were present in Irgm1 KO mice, even without dextran sodium sulfate exposure, and were associated with impaired mitophagy and autophagy in Irgm1 KO intestinal cells (including Paneth cells). This was manifested by frequent tubular and swollen mitochondria and increased LC3-positive autophagic structures. Interestingly, these LC3-positive structures often contained Paneth cell granules. These results suggest that Irgm1 modulates acute inflammatory responses in the mouse intestine, putatively through the regulation of gut autophagic processes, that may be pivotal for proper Paneth cell functioning.