title: IL-7Rα Expression Regulates Murine Dendritic Cell Sensitivity to Thymic Stromal Lymphopoietin.
abstract: Thymic stromal lymphopoietin (TSLP) and IL-7 are related cytokines that mediate growth and differentiation events in the immune system. They signal through IL-7Rα-containing receptors. Target cells of TSLP in Th2 responses include CD4 T cells and dendritic cells (DCs). Although it has been reported that expression of TSLP receptor (TSLPR) on CD4 T cells is required for OVA-induced lung inflammation, DCs have also been shown to be target cells of TSLP. In this study, we show that murine ex vivo splenic DCs are unresponsive to TSLP, as they fail to phosphorylate STAT5, but in vitro overnight culture, especially in presence of IL-4, renders DCs responsive to both TSLP and IL-7. This induced responsiveness is accompanied by dramatic upregulation of IL-7Rα on DCs with little change in expression of TSLPR or of γcIn splenic DCs, the induction of IL-7Rα occurs mainly in CD8-DCs. In vivo, we found that IL-4 has a differential regulatory role on expression of IL-7Rα depending on the cell type; IL-4 decreases IL-7Rα expression on CD4 T cells whereas it upregulates the expression on DCs. Our results indicate that the induction of IL-7Rα expression on DCs is critical for TSLP responsiveness and that IL-4 can upregulate IL-7Rα on DCs.
authors.affiliation: Faculty of Medicine and Life Sciences, University of Tampere, 33520 Tampere, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Kummola
authors.affiliation: Faculty of Medicine and Life Sciences, University of Tampere, 33520 Tampere, Finland.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Ortutay
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Stephane
authors.initials: S
authors.lastname: Caucheteux
authors.affiliation: Biomeditech, University of Tampere, 33014 Tampere, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Hämäläinen
authors.affiliation: Biomeditech, University of Tampere, 33014 Tampere, Finland.
authors.forename: Saara
authors.initials: S
authors.lastname: Aittomäki
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Ryoji
authors.identifier: 0000-0001-7621-2753
authors.initials: R
authors.lastname: Yagi
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Biomeditech, University of Tampere, 33014 Tampere, Finland.|Department of Dermatology, Tampere University Hospital, 33521 Tampere, Finland; and.
authors.forename: Marko
authors.identifier: 0000-0002-7541-3921
authors.initials: M
authors.lastname: Pesu
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: William E
authors.initials: WE
authors.lastname: Paul
authors.affiliation: Faculty of Medicine and Life Sciences, University of Tampere, 33520 Tampere, Finland; Ilkka.junttila@uta.fi.|Fimlab Laboratories, 33520 Tampere, Finland.
authors.forename: Ilkka S
authors.initials: IS
authors.lastname: Junttila
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015851:Interleukin-7 / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation; D020395:Receptors, Interleukin-7 / Q000235:genetics* / Q000276:immunology*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D015851:Interleukin-7; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; C415350:interleukin-7 receptor, alpha chain; C576410:interleukin-7, mouse; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse