Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated immune cascade

Juan Manuel Leyva-Castillo, Pierre Hener, Paula Michea, Hajime Karasuyama, Susan Chan, Vassili Soumelis and Mei Li ()
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Juan Manuel Leyva-Castillo: 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
Pierre Hener: 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
Paula Michea: Institut National de la Santé et de la Recherche Médicale U932
Hajime Karasuyama: Tokyo Medical and Dental University Graduate School
Susan Chan: 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
Vassili Soumelis: Institut National de la Santé et de la Recherche Médicale U932
Mei Li: 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

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms3847

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