In:
The Journal of Immunology, The American Association of Immunologists, Vol. 184, No. 1_Supplement ( 2010-04-01), p. 36.33-36.33
Abstract:
An organized 3D thymic epithelial cell (TEC) meshwork is crucial for T-lymphocyte development. Expansion of thymic epithelial cystic cavities represents disruption of this 3D-structure. Abnormal culture, lacking lympho-stromal interactions, thymic aging, and gene mutation induce 2D-thymus cysts. Since germline FoxN1 gene mutation develops a 2D-cystic thymic rudiment, while abnormal culture caused 2D-thymus cyst-lining was reported to be non-FoxN1-dependent, it is unclear whether loss of FoxN1 promotes generation of thymic cysts, whether FoxN1 regulates maintenance of the 3D-thymus structure. Using loxP-floxed FoxN1 mouse model, we demonstrated that deletion of FoxN1 in K-14 promoter-driven epithelium induced loss of 3D-thymus medullary structure by producing a large number of alveolus-like 2D-epithelial cysts. The cyst-lining epithelium showed immature TEC phenotype by expressing Cld3,4 and K8, but low levels of MHC-II and K5. These 2D-thymus cysts expanded with ages, associated with reduced UEA-1+ and Aire+ TECs, and FoxN1 mutant Cld3,4+ TECs cannot develop mature medullary TECs. Meanwhile, K14-specific FoxN1 deletion sufficiently induced hair follicle defect and caused FoxN1-null nude phenotype in the skin, but did not cause athymia. These findings provide new insight into gene regulation on 3D-thymus epithelial structure and separate roles of FoxN1 in the thymus and skin. Supported by the NIH grants (R01AI081995, R21AG031880, and R21AI079747) to D-M S.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.184.Supp.36.33
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2010
detail.hit.zdb_id:
1475085-5
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