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

Nat Commun. 2013:4:2847. doi: 10.1038/ncomms3847.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basophils / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cytokines / genetics
  • Cytokines / immunology*
  • Dendritic Cells / immunology
  • Female
  • Interleukin-4 / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Skin / cytology
  • Skin / immunology*
  • Th2 Cells / immunology*
  • Thymic Stromal Lymphopoietin

Substances

  • Cytokines
  • Interleukin-4
  • Thymic Stromal Lymphopoietin
  • TSLP protein, mouse