Publication:
Autophagy in the thymic epithelium is dispensable for the development of self-tolerance in a novel mouse model

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Issued Date

2012

Resource Type

Article

File Type

application/pdf

ISSN

19326203

DOI

10.1371/journal.pone.0038933

Other identifier(s)

2-s2.0-84862490479

Rights Holder(s)

Scopus

Bibliographic Citation

PLoS ONE. Vol 7, No.6 (2012), p.-

Suggested Citation

Sukseree S., Mildner M., Rossiter H., Pammer J., Zhang C.-F., Watanapokasin R., Tschachler E., Eckhart L. Autophagy in the thymic epithelium is dispensable for the development of self-tolerance in a novel mouse model. PLoS ONE. Vol 7, No.6 (2012), p.-. doi:10.1371/journal.pone.0038933 Retrieved from: https://hdl.handle.net/20.500.14740/7028

Title

Autophagy in the thymic epithelium is dispensable for the development of self-tolerance in a novel mouse model

Author(s)

Sukseree S.
 Mildner M.
 Rossiter H.
 Pammer J.
 Zhang C.-F.
 Watanapokasin R.
 Tschachler E.
 Eckhart L.

Abstract

The thymic epithelium plays critical roles in the positive and negative selection of T cells. Recently, it was proposed that autophagy in thymic epithelial cells is essential for the induction of T cell tolerance to self antigens and thus for the prevention of autoimmune diseases. Here we have tested this hypothesis using mouse models in which autophagy was blocked specifically in epithelial cells expressing keratin 14 (K14), including the precursor of thymic epithelial cells. While the thymic epithelial cells of mice carrying the floxed Atg7 gene (ATG7 f/f) showed a high level of autophagy, as determined by LC3 Western blot analysis and fluorescence detection of the recombinant green fluorescent protein (GFP)-LC3 reporter protein on autophagosomes, autophagy in the thymic epithelium was efficiently suppressed by deletion of the Atg7 gene using the Cre-loxP system (ATG7 f/f K14-Cre). Suppression of autophagy led to the massive accumulation of p62/sequestosome 1 (SQSTM1) in thymic epithelial cells. However, the structure of the thymic epithelium as well as the organization and the size of the thymus were not altered in mutant mice. The ratio of CD4 to CD8-positive T cells, as well as the frequency of activated (CD69+) CD4 T cells in lymphoid organs, did not differ between mice with autophagy-competent and autophagy-deficient thymic epithelium. Inflammatory infiltrating cells, potentially indicative of autoimmune reactions, were present in the liver, lung, and colon of a similar fraction of ATG7 f/f and ATG7 f/f K14-Cre mice. In contrast to previously reported mice, that had received an autophagy-deficient thymus transplant, ATG7 f/f K14-Cre mice did not suffer from autoimmunity-induced weight loss. In summary, the results of this study suggest that autophagy in the thymic epithelium is dispensable for negative selection of autoreactive T cells. © 2012 Sukseree et al.

Subject(s)

CD4 antigen
 CD69 antigen
 CD8 antigen
 Cell protein
 Cre recombinase
 Cytokeratin 14
 Green fluorescent protein
 Microtubule associated protein
 Protein LC3
 Protein loxP
 Protein p62
 Protein SQSTM1
 Unclassified drug
 Animal cell
 Animal experiment
 Animal model
 Animal tissue
 Article
 Atg7 gene
 Autoimmunity
 Autophagosome
 Autophagy
 CD4+ T lymphocyte
 CD8+ T lymphocyte
 Cell size
 Cell structure
 Controlled study
 Embryo
 Epithelium cell
 Experimental model
 Female
 Fluorescence analysis
 Gene
 Gene deletion
 Immunocompetence
 Immunological tolerance
 Inflammatory infiltrate
 Intestine cell
 Liver cell
 Lung alveolus cell
 Lymphocyte activation
 Mouse
 Nonhuman
 Promoter region
 Protein expression
 Thymus
 Western blotting
 Animals
 Autophagy
 Blotting, Western
 Female
 Green Fluorescent Proteins
 Mice
 Models, Animal
 Self Tolerance
 Thymus Gland

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URI

https://hdl.handle.net/20.500.14740/7028

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Scopus: Year 1983-2021

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