Abnormal activation of autophagy-induced crinophagy in Paneth cells from patients with Crohn's disease

Gastroenterology. 2012 May;142(5):1097-1099.e4. doi: 10.1053/j.gastro.2012.01.031. Epub 2012 Jan 28.


Autophagy-related 16 like-1 (ATG16L-1), immunity-related GTPase-M (IRGM), and nucleotide-binding oligomerization domain-containing 2 (NOD2) regulate autophagy, and variants in these genes have been associated with predisposition to Crohn's disease (CD). However, little is known about the role of autophagy in CD. Intestinal biopsies from untreated pediatric patients with CD, celiac disease, or ulcerative colitis were analyzed by immunohistochemistry and electron microscopy. We observed that autophagy was specifically activated in Paneth cells from patients with CD, independently of mucosal inflammation or disease-associated variants of ATG16L1 or IRGM. In these cells, activation of autophagy was associated with a significant decrease in number of secretory granules and features of crinophagy. These observations might account for the disorganization of secretory granules previously reported in Paneth cells from patients with CD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / physiology*
  • Autophagy-Related Proteins
  • Carrier Proteins / genetics
  • Child
  • Crohn Disease / pathology*
  • Female
  • GTP-Binding Proteins / genetics
  • Humans
  • Infant
  • Male
  • Microtubule-Associated Proteins / analysis
  • Nod2 Signaling Adaptor Protein / genetics
  • Paneth Cells / ultrastructure*
  • Polymorphism, Single Nucleotide
  • Secretory Vesicles / physiology*


  • ATG16L1 protein, human
  • Autophagy-Related Proteins
  • Carrier Proteins
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • GTP-Binding Proteins
  • IRGM protein, human