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

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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
    Institut Curie)

  • Hajime Karasuyama

    (Tokyo Medical and Dental University Graduate School
    JST, CREST, 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
    Institut Curie)

  • 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
    University of Strasbourg Institute for Advanced Study (USIAS)
    Freiburg Institute for Advanced Studies (FRIAS))

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.

Suggested Citation

  • Juan Manuel Leyva-Castillo & Pierre Hener & Paula Michea & Hajime Karasuyama & Susan Chan & Vassili Soumelis & Mei Li, 2013. "Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated immune cascade," Nature Communications, Nature, vol. 4(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3847
    DOI: 10.1038/ncomms3847
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    Cited by:

    1. Qingtai Su & Aurélie Bouteau & Jacob Cardenas & Balaji Uthra & Yuanyaun Wang & Cynthia Smitherman & Jinghua Gu & Botond Z Igyártó, 2020. "Brief communication: Long-term absence of Langerhans cells alters the gene expression profile of keratinocytes and dendritic epidermal T cells," PLOS ONE, Public Library of Science, vol. 15(1), pages 1-9, January.
    2. Justine Segaud & Wenjin Yao & Pierre Marschall & François Daubeuf & Christine Lehalle & Beatriz German & Pierre Meyer & Pierre Hener & Cécile Hugel & Eric Flatter & Marine Guivarch & Laetitia Clauss &, 2022. "Context-dependent function of TSLP and IL-1β in skin allergic sensitization and atopic march," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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