Skip to main content
Journal cover image

Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice.

Publication ,  Journal Article
Rogala, AR; Schoenborn, AA; Fee, BE; Cantillana, VA; Joyce, MJ; Gharaibeh, RZ; Roy, S; Fodor, AA; Sartor, RB; Taylor, GA; Gulati, AS
Published in: Dis Model Mech
February 7, 2018

Crohn's disease (CD) represents a chronic inflammatory disorder of the intestinal tract. Several susceptibility genes have been linked to CD, though their precise role in the pathogenesis of this disorder remains unclear. Immunity-related GTPase M (IRGM) is an established risk allele in CD. We have shown previously that conventionally raised (CV) mice lacking the IRGM ortholog, Irgm1 exhibit abnormal Paneth cells (PCs) and increased susceptibility to intestinal injury. In the present study, we sought to utilize this model system to determine if environmental conditions impact these phenotypes, as is thought to be the case in human CD. To accomplish this, wild-type and Irgm1-/- mice were rederived into specific pathogen-free (SPF) and germ-free (GF) conditions. We next assessed how these differential housing environments influenced intestinal injury patterns, and epithelial cell morphology and function in wild-type and Irgm1-/- mice. Remarkably, in contrast to CV mice, SPF Irgm1-/- mice showed only a slight increase in susceptibility to dextran sodium sulfate-induced inflammation. SPF Irgm1-/- mice also displayed minimal abnormalities in PC number and morphology, and in antimicrobial peptide expression. Goblet cell numbers and epithelial proliferation were also unaffected by Irgm1 in SPF conditions. No microbial differences were observed between wild-type and Irgm1-/- mice, but gut bacterial communities differed profoundly between CV and SPF mice. Specifically, Helicobacter sequences were significantly increased in CV mice; however, inoculating SPF Irgm1-/- mice with Helicobacter hepaticus was not sufficient to transmit a pro-inflammatory phenotype. In summary, our findings suggest the impact of Irgm1-deficiency on susceptibility to intestinal inflammation and epithelial function is critically dependent on environmental influences. This work establishes the importance of Irgm1-/- mice as a model to elucidate host-environment interactions that regulate mucosal homeostasis and intestinal inflammatory responses. Defining such interactions will be essential for developing novel preventative and therapeutic strategies for human CD.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Dis Model Mech

DOI

EISSN

1754-8411

Publication Date

February 7, 2018

Volume

11

Issue

2

Location

England

Related Subject Headings

  • Specific Pathogen-Free Organisms
  • Phenotype
  • Paneth Cells
  • Mice, Knockout
  • Intestines
  • Inflammation
  • Helicobacter
  • Goblet Cells
  • Genotype
  • Gastrointestinal Microbiome
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rogala, A. R., Schoenborn, A. A., Fee, B. E., Cantillana, V. A., Joyce, M. J., Gharaibeh, R. Z., … Gulati, A. S. (2018). Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice. Dis Model Mech, 11(2). https://doi.org/10.1242/dmm.031070
Rogala, Allison R., Alexi A. Schoenborn, Brian E. Fee, Viviana A. Cantillana, Maria J. Joyce, Raad Z. Gharaibeh, Sayanty Roy, et al. “Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice.Dis Model Mech 11, no. 2 (February 7, 2018). https://doi.org/10.1242/dmm.031070.
Rogala AR, Schoenborn AA, Fee BE, Cantillana VA, Joyce MJ, Gharaibeh RZ, et al. Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice. Dis Model Mech. 2018 Feb 7;11(2).
Rogala, Allison R., et al. “Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice.Dis Model Mech, vol. 11, no. 2, Feb. 2018. Pubmed, doi:10.1242/dmm.031070.
Rogala AR, Schoenborn AA, Fee BE, Cantillana VA, Joyce MJ, Gharaibeh RZ, Roy S, Fodor AA, Sartor RB, Taylor GA, Gulati AS. Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice. Dis Model Mech. 2018 Feb 7;11(2).
Journal cover image

Published In

Dis Model Mech

DOI

EISSN

1754-8411

Publication Date

February 7, 2018

Volume

11

Issue

2

Location

England

Related Subject Headings

  • Specific Pathogen-Free Organisms
  • Phenotype
  • Paneth Cells
  • Mice, Knockout
  • Intestines
  • Inflammation
  • Helicobacter
  • Goblet Cells
  • Genotype
  • Gastrointestinal Microbiome