title: Abnormal activation of autophagy-induced crinophagy in Paneth cells from patients with Crohn's disease.
abstract: 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.
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Thachil
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hugot
authors.forename: Brigitte
authors.initials: B
authors.lastname: Arbeille
authors.forename: Régine
authors.initials: R
authors.lastname: Paris
authors.forename: Alain
authors.initials: A
authors.lastname: Grodet
authors.forename: Michel
authors.initials: M
authors.lastname: Peuchmaur
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
authors.forename: Frédérick
authors.initials: F
authors.lastname: Barreau
authors.forename: Eric
authors.initials: E
authors.lastname: Ogier-Denis
authors.forename: Dominique
authors.initials: D
authors.lastname: Berrebi
authors.forename: Jérôme
authors.initials: J
authors.lastname: Viala
mesh_terms: D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D003424:Crohn Disease / Q000473:pathology*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D019879:Paneth Cells / Q000648:ultrastructure*; D020641:Polymorphism, Single Nucleotide; D022142:Secretory Vesicles / Q000502:physiology*
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D019204:GTP-Binding Proteins; C513539:IRGM protein, human