Characterization of the thymic IL-7 niche in vivo
Autor: | Ana Cumano, Odile Richard-Le Goff, Ana Patricia Sousa, Nuno L. Alves, Richard L. Boyd, Vera S. G. Ribeiro, Allison Bordack, Gérard Eberl, Lucie Peduto, James P. Di Santo, Ann P. Chidgey, Francina Langa Vives, Nicholas D. Huntington |
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Přispěvatelé: | Cytokines et Développement Lymphoïde, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Développement des Lymphocytes, Centre d'Ingénierie génétique murine - Mouse Genetics Engineering Center (CIGM), Institut Pasteur [Paris] (IP), Développement des Tissus Lymphoïdes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Monash Immunology and Stem Cell Laboratories (MISCL), Monash University [Clayton], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS) |
Rok vydání: | 2009 |
Předmět: |
Genetically modified mouse
Chromosomes Artificial Bacterial Chemokine MESH: Chromosomes Artificial Bacterial MESH: Mice Transgenic medicine.medical_treatment T cell Mice Transgenic Thymus Gland Biology Polymerase Chain Reaction Mice 03 medical and health sciences 0302 clinical medicine Genes Reporter In vivo medicine Animals MESH: Animals RNA Messenger MESH: Mice Cells Cultured MESH: RNA Messenger 030304 developmental biology 0303 health sciences Thymic involution Multidisciplinary Interleukin-7 MESH: Genes Reporter CCL19 Epithelial Cells MESH: Polymerase Chain Reaction MESH: Thymus Gland Biological Sciences Molecular biology MESH: Interleukin-7 Luminescent Proteins Cytokine medicine.anatomical_structure MESH: Epithelial Cells biology.protein [SDV.IMM]Life Sciences [q-bio]/Immunology MESH: Luminescent Proteins CCL25 MESH: Cells Cultured 030215 immunology |
Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2009, 106 (5), pp.1512-7. ⟨10.1073/pnas.0809559106⟩ Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2009, 106 (5), pp.1512-7. ⟨10.1073/pnas.0809559106⟩ |
ISSN: | 1091-6490 0027-8424 |
DOI: | 10.1073/pnas.0809559106 |
Popis: | 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. |
Databáze: | OpenAIRE |
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