Characterization of the thymic IL-7 niche in vivo

• DOI: 10.1073/pnas.0809559106
• Publication Date: 2009-01-22T02:40:22Z
• Authors: Nuno L. Alves; Odile Richard-Le ...; Nicholas D. Hunti...; Ana Patricia Sousa; Vera S. G. Ribeiro; Allison Bordack; Francina Langa Vives; Lucie Peduto; Ann Chidgey; Ana Cumano; Richard Boyd; Gerard Eberl; James P. Di Santo
• Keywords: Chromosomes, Artificial, Bacterial; MESH: Chromosomes, Artificial, Bacterial; [SDV.IMM] Life Sciences [q-bio]/Immunology; MESH: Mice, Transgenic; Mice, Transgenic; Thymus Gland; Polymerase Chain Reaction; Mice; 03 medical and health sciences; 0302 clinical medicine; Genes, Reporter; Animals; MESH: Animals; RNA, Messenger; MESH: Mice; Cells, Cultured; MESH: RNA, Messenger; Interleukin-7; MESH: Genes, Reporter; MESH: Polymerase Chain Reaction; Epithelial Cells; MESH: Thymus Gland; MESH: Interleukin-7; Luminescent Proteins; MESH: Epithelial Cells; [SDV.IMM]Life Sciences [q-bio]/Immunology; MESH: Luminescent Proteins; MESH: Cells, Cultured

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 ofIl7transcripts (IL-7hicells). IL-7hiTECs 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-7hicells localize to the cortico-medullary junction and display traits of both cortical and medullary TECs. Interestingly, the frequency of IL-7hicells 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.