期刊
JOURNAL OF IMMUNOLOGY
卷 190, 期 12, 页码 6173-6179出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1202573
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类别
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [21590531, 24790468]
- Fujiwara Memorial Foundation
- Leave a Nest Grant MBL Award
- Shimizu Foundation for Immunology and Neuroscience
- BioLegend/Tomy Digital Biology Young Scientist Research Award
- Grants-in-Aid for Scientific Research [25111504, 24790468, 21590531, 24790469, 25460589] Funding Source: KAKEN
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 ab and gamma delta 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, gamma delta T cells were absent from the fetal thymus and epidermis of IL-7(f/f) FoxN1-Cre mice. Furthermore, TCR gamma delta(+) 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 alpha beta and gamma delta 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 gamma delta T cell development. This study also demonstrates that IL-7 produced in the thymus is essential for the development of gamma delta IELs and indicates the thymic origin of gamma delta IELs.
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