title: An alternative NFAT-activation pathway mediated by IL-7 is critical for early thymocyte development.
abstract: Interleukin 7 (IL-7) has a critical role in the development of early CD4(-)CD8(-) double-negative (DN) thymocytes. Although the transcription factor STAT5 is an important component of IL-7 signaling, differences in the phenotypes of mice deficient in STAT5, IL-7, IL-7 receptor alpha (IL-7rα) or the kinase Jak3 suggest the existence of STAT5-independent IL-7 signaling. Here we found that IL-7-Jak3 signals activated the transcription factor NFATc1 in DN thymocytes by phosphorylating Tyr371 in the regulatory region of NFATc1. This NFAT-activation pathway was critical for the survival and development of DN thymocytes, as deficiency in NFATc1 blocked thymocyte development at the DN1 stage, leading to T cell lymphopenia. In addition, our results demonstrated a cooperative function for NFATc1 and STAT5 in guiding thymocyte development in response to IL-7 signals.
authors.affiliation: Department of Molecular Pathology, Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors.forename: Amiya K
authors.initials: AK
authors.lastname: Patra
authors.forename: Andris
authors.initials: A
authors.lastname: Avots
authors.forename: René P
authors.initials: RP
authors.lastname: Zahedi
authors.forename: Thomas
authors.initials: T
authors.lastname: Schüler
authors.forename: Albert
authors.initials: A
authors.lastname: Sickmann
authors.forename: Ursula
authors.initials: U
authors.lastname: Bommhardt
authors.forename: Edgar
authors.initials: E
authors.lastname: Serfling
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D015851:Interleukin-7 / Q000235:genetics* / Q000276:immunology; D053616:Janus Kinase 3 / Q000235:genetics / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors / Q000172:deficiency / Q000235:genetics*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D060168:Thymocytes / Q000166:cytology* / Q000276:immunology; D014158:Transcription, Genetic
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D015851:Interleukin-7; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; C576410:interleukin-7, mouse; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3