Characterization of the thymic IL-7 niche in vivo.
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.
Alves
Nuno L
NL
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.
Richard-Le Goff
Odile
O
Huntington
Nicholas D
ND
Sousa
Ana Patricia
AP
Ribeiro
Vera S G
VS
Bordack
Allison
A
Vives
Francina Langa
FL
Peduto
Lucie
L
Chidgey
Ann
A
Cumano
Ana
A
Boyd
Richard
R
Eberl
Gerard
G
Di Santo
James P
JP
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*
D015851:Interleukin-7; D008164:Luminescent Proteins; D012333:RNA, Messenger