title: Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated immune cascade.
abstract: Thymic stromal lymphopoietin (TSLP) has emerged as a key initiator in Th2 immune responses, but the TSLP-driven immune cascade leading to Th2 initiation remains to be delineated. Here, by dissecting the cellular network triggered by mouse skin TSLP in vivo, we uncover that TSLP-promoted IL-4 induction in CD4(+) T cells in skin-draining lymph nodes is driven by an orchestrated 'DC-T-Baso-T' cascade, which represents a sequential cooperation of dendritic cells (DCs), CD4(+) T cells and basophils. Moreover, we reveal that TSLP-activated DCs prime naive CD4(+) T cells to produce IL-3 via OX40L signalling and demonstrate that the OX40L-IL-3 axis has a critical role in mediating basophil recruitment, CD4(+) T-cell expansion and Th2 priming. These findings thus add novel insights into the cellular network and signal axis underlying the initiation of Th2 immune responses.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique UMR7104/Institut National de la Santé et de la Recherche Médicale U964/Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Leyva-Castillo
authors.forename: Pierre
authors.initials: P
authors.lastname: Hener
authors.forename: Paula
authors.initials: P
authors.lastname: Michea
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
authors.forename: Susan
authors.initials: S
authors.lastname: Chan
authors.forename: Vassili
authors.initials: V
authors.lastname: Soumelis
authors.forename: Mei
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D001491:Basophils / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012867:Skin / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse