title: Characterization of the thymic IL-7 niche in vivo.
abstract: The thymus represents the "cradle" for T cell development, with thymic stroma providing multiple soluble and membrane cues to developing thymocytes. Although IL-7 is recognized as an essential factor for thymopoiesis, the "environmental niche" of thymic IL-7 activity remains poorly characterized in vivo. Using bacterial artificial chromosome transgenic mice in which YFP is under control of IL-7 promoter, we identify a subset of thymic epithelial cells (TECs) that co-express YFP and high levels of Il7 transcripts (IL-7(hi) cells). IL-7(hi) TECs arise during early fetal development, persist throughout life, and co-express homeostatic chemokines (Ccl19, Ccl25, Cxcl12) and cytokines (Il15) that are critical for normal thymopoiesis. In the adult thymus, IL-7(hi) cells localize to the cortico-medullary junction and display traits of both cortical and medullary TECs. Interestingly, the frequency of IL-7(hi) cells decreases with age, suggesting a mechanism for the age-related thymic involution that is associated with declining IL-7 levels. Our temporal-spatial analysis of IL-7-producing cells in the thymus in vivo suggests that thymic IL-7 levels are dynamically regulated under distinct physiological conditions. This IL-7 reporter mouse provides a valuable tool to further dissect the mechanisms that govern thymic IL-7 expression in vivo.
authors.affiliation: Cytokines and Lymphoid Development Unit, Lymphocyte Development Unit, Plate-Forme Technologique Centre d'Ingénierie Génétique Murine, and Laboratory of Lymphoid Tissue Development, Institut Pasteur, Paris, France.
authors.forename: Nuno L
authors.initials: NL
authors.lastname: Alves
authors.forename: Odile
authors.initials: O
authors.lastname: Richard-Le Goff
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Huntington
authors.forename: Ana Patricia
authors.initials: AP
authors.lastname: Sousa
authors.forename: Vera S G
authors.initials: VS
authors.lastname: Ribeiro
authors.forename: Allison
authors.initials: A
authors.lastname: Bordack
authors.forename: Francina Langa
authors.initials: FL
authors.lastname: Vives
authors.forename: Lucie
authors.initials: L
authors.lastname: Peduto
authors.forename: Ann
authors.initials: A
authors.lastname: Chidgey
authors.forename: Ana
authors.initials: A
authors.lastname: Cumano
authors.forename: Richard
authors.initials: R
authors.lastname: Boyd
authors.forename: Gerard
authors.initials: G
authors.lastname: Eberl
authors.forename: James P
authors.initials: JP
authors.lastname: Di Santo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D022202:Chromosomes, Artificial, Bacterial; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D017930:Genes, Reporter; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D015851:Interleukin-7; D008164:Luminescent Proteins; D012333:RNA, Messenger