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- Title
Autoimmunity associated with chemically induced thymic dysplasia.
- Authors
Daisuke Nagakubo; Swann, Jeremy B.; Birmelin, Stefanie; Boehm, Thomas
- Abstract
Autoimmune and inflammatory conditions are frequent complications in patients with reduced numbers of T cells. Here, we describe a mouse model of thymic stromal dysplasia resulting in peripheral T-cell lymphopenia. In Foxn1:CFP-NTR transgenic mice, the bacterial nitroreductase enzyme is expressed in thymic epithelial cells and converts the prodrug CB1954 into a cytotoxic agent. This strategy enables titratable and durable destruction of thymopoietic tissue in early embryogenesis. Our results indicate that the resulting low levels of thymic capacity for T-cell production create a predisposition for the development of a complex autoimmune syndrome, chiefly characterized by inflammatory bowel disease and lymphocytic organ infiltrations. We conclude that the Foxn1:CFP-NTR transgenic mouse strain represents a suitable animal model to optimize established clinical protocols, such as thymus transplantation, to correct various forms of thymic dysplasia and to explore novel treatment options.
- Subjects
AUTOIMMUNITY; T cells; LYMPHOPENIA; NITROREDUCTASES; INFLAMMATORY bowel diseases; LABORATORY mice
- Publication
International Immunology, 2017, Vol 29, Issue 8, p385
- ISSN
0953-8178
- Publication type
Article
- DOI
10.1093/intimm/dxx048