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Publication : IL-7 produced by thymic epithelial cells plays a major role in the development of thymocytes and TCR??+ intraepithelial lymphocytes.

First Author  Shitara S Year  2013
Journal  J Immunol Volume  190
Issue  12 Pages  6173-9
PubMed ID  23686483 Mgi Jnum  J:204843
Mgi Id  MGI:5543548 Doi  10.4049/jimmunol.1202573
Citation  Shitara S, et al. (2013) IL-7 produced by thymic epithelial cells plays a major role in the development of thymocytes and TCRgammadelta+ intraepithelial lymphocytes. J Immunol 190(12):6173-9
abstractText  IL-7 is a cytokine essential for T cell development and survival. However, the local function of IL-7 produced by thymic epithelial cells (TECs) is poorly understood. To address this question, we generated IL-7-floxed mice and crossed them with FoxN1 promoter-driven Cre (FoxN1-Cre) mice to establish knockout mice conditionally deficient for the expression of IL-7 by TECs. We found that alphabeta and gammadelta T cells were significantly reduced in the thymus of IL-7(f/f) FoxN1-Cre mice. Proportion of mature single-positive thymocytes was increased. In lymph nodes and the spleen, the numbers of T cells were partially restored in IL-7(f/f) FoxN1-Cre mice. In addition, gammadelta T cells were absent from the fetal thymus and epidermis of IL-7(f/f) FoxN1-Cre mice. Furthermore, TCRgammadelta(+) intraepithelial lymphocytes (IELs) were significantly decreased in the small intestines of IL-7(f/f) FoxN1-Cre mice. To evaluate the function of IL-7 produced in the intestine, we crossed the IL-7(f/f) mice with villin promoter-driven Cre (Vil-Cre) mice to obtain the mice deficient in IL-7 production from intestinal epithelial cells. We observed that alphabeta and gammadelta IELs of IL-7(f/f) Vil-Cre mice were comparable to control mice. Collectively, our results suggest that TEC-derived IL-7 plays a major role in proliferation, survival, and maturation of thymocytes and is indispensable for gammadelta T cell development. This study also demonstrates that IL-7 produced in the thymus is essential for the development of gammadelta IELs and indicates the thymic origin of gammadelta IELs.
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