title: IL-7 produced by thymic epithelial cells plays a major role in the development of thymocytes and TCRγδ+ intraepithelial lymphocytes.
abstract: 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 αβ and γδ 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, γδ T cells were absent from the fetal thymus and epidermis of IL-7(f/f) FoxN1-Cre mice. Furthermore, TCRγδ(+) 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 αβ and γδ 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 γδ T cell development. This study also demonstrates that IL-7 produced in the thymus is essential for the development of γδ IELs and indicates the thymic origin of γδ IELs.
authors.affiliation: Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Shitara
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hara
authors.forename: Bingfei
authors.initials: B
authors.lastname: Liang
authors.forename: Keisuke
authors.initials: K
authors.lastname: Wagatsuma
authors.forename: Saulius
authors.initials: S
authors.lastname: Zuklys
authors.forename: Georg A
authors.initials: GA
authors.lastname: Holländer
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakase
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.forename: Shizue
authors.initials: S
authors.lastname: Tani-ichi
authors.forename: Koichi
authors.initials: K
authors.lastname: Ikuta
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D015851:Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D015851:Interleukin-7; D016692:Receptors, Antigen, T-Cell, gamma-delta