期刊
NATURE COMMUNICATIONS
卷 4, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms3847
关键词
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资金
- l'Agence Nationale de la Recherche (ANR)
- Fondation Simone et Cino del Duca (Institut de France)
- Societe Francaise d'Allergologie
- Association pour la Recherche a l'IGBMC
- Institut Curie, Fondation pour la Recherche Medicale
- JST, CREST
- Centre National de la Recherche Scientifique (CNRS)
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Universite de Strasbourg (UDS)
- Grants-in-Aid for Scientific Research [24390093] Funding Source: KAKEN
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(+) Tcells 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.
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