title: Targeted deletion of Atg5 reveals differential roles of autophagy in keratin K5-expressing epithelia.
abstract: Autophagy contributes to the homeostasis of many tissues, yet its role in epithelia is incompletely understood. A recent report proposed that Atg5-dependent autophagy in thymic epithelial cells is essential for their function in the negative selection of self-reactive T-cells and, thus, for the suppression of tissue inflammation. Here we crossed mice carrying floxed alleles of the Atg5 gene with mice expressing the Cre recombinase under the control of the keratin K5 promoter to suppress autophagy in all K5-positive epithelia. The efficiency of autophagy abrogation was confirmed by immunoanalyses of LC3, which was converted to the autophagy-associated LC3-II form in normal but not Atg5-deficient cells, and of p62, which accumulated in Atg5-deficient cells. Mice carrying the epithelium-specific deletion of Atg5 showed normal weight gain, absence of tissue inflammation, and a normal morphology of the thymic epithelium. By contrast, autophagy-deficient epithelial cells of the preputial gland showed aberrant eosinophilic staining in histology and premature degradation of nuclear DNA during terminal differentiation. Taken together, the results of this study suggest that autophagy is dispensable for the suppression of autoimmunity by thymic epithelial cells but essential for normal differentiation of the preputial gland in mice.
authors.affiliation: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Supawadee
authors.initials: S
authors.lastname: Sukseree
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Rossiter
authors.forename: Michael
authors.initials: M
authors.lastname: Mildner
authors.forename: Johannes
authors.initials: J
authors.lastname: Pammer
authors.forename: Maria
authors.initials: M
authors.lastname: Buchberger
authors.forename: Florian
authors.initials: F
authors.lastname: Gruber
authors.forename: Ramida
authors.initials: R
authors.lastname: Watanapokasin
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
authors.forename: Leopold
authors.initials: L
authors.lastname: Eckhart
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001343:Autophagy / Q000235:genetics / Q000276:immunology*; D000071187:Autophagy-Related Protein 5; D001835:Body Weight / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D017353:Gene Deletion; D018390:Gene Targeting; D053569:Keratin-15; D053555:Keratin-5 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D015430:Weight Gain / Q000235:genetics
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D053569:Keratin-15; D053555:Keratin-5; C492053:Krt15 protein, mouse; D008869:Microtubule-Associated Proteins