title: Requirement of Stat3 Signaling in the Postnatal Development of Thymic Medullary Epithelial Cells.
abstract: Thymic medullary regions are formed in neonatal mice as islet-like structures, which increase in size over time and eventually fuse a few weeks after birth into a continuous structure. The development of medullary thymic epithelial cells (TEC) is dependent on NF-κB associated signaling though other signaling pathways may contribute. Here, we demonstrate that Stat3-mediated signals determine medullary TEC cellularity, architectural organization and hence the size of the medulla. Deleting Stat3 expression selectively in thymic epithelia precludes the postnatal enlargement of the medulla retaining a neonatal architecture of small separate medullary islets. In contrast, loss of Stat3 expression in cortical TEC neither affects the cellularity or organization of the epithelia. Activation of Stat3 is mainly positioned downstream of EGF-R as its ablation in TEC phenocopies the loss of Stat3 expression in these cells. These results indicate that Stat3 meditated signal via EGF-R is required for the postnatal development of thymic medullary regions.
authors.affiliation: Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.|Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Rumi
authors.initials: R
authors.lastname: Satoh
authors.affiliation: Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.|Laboratory for Immune Crosstalk, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Kakugawa
authors.affiliation: Laboratory for Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokoham, Japan.
authors.forename: Takuwa
authors.initials: T
authors.lastname: Yasuda
authors.affiliation: Laboratory for Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokoham, Japan.
authors.forename: Hisahiro
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Medicine I, Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Sibilia
authors.affiliation: Division of Cell Regeneration and Transplantation, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Katsura
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ben
authors.initials: B
authors.lastname: Levi
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Jakub
authors.initials: J
authors.lastname: Abramson
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Koseki
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.affiliation: Department of Molecular Cell Biology and Department of Immunology, Leiden University Medical Center, RA Leiden, the Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: van Ewijk
authors.affiliation: Laboratory of Pediatric Immunology, Center for Biomedicine, University of Basel, and the University Children's Hospital, Basel, Switzerland.|Laboratory of Developmental Immunology Weatherall Institute of Molecular Medicine and Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Hollander
authors.affiliation: Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.|Department of Immunology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamoto
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D047108:Embryonic Development; D004847:Epithelial Cells; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D060168:Thymocytes / Q000378:metabolism; D013950:Thymus Gland / Q000254:growth & development / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C541485:EGFR protein, mouse; D066246:ErbB Receptors