DC-derived TSLP promotes Th2 polarization in LPS-primed allergic airway inflammation

Yanlu Zhang, Xueping Zhou, Baohua Zhou

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Thymic stromal lymphopoietin (TSLP) plays important roles in the pathogenesis of allergic diseases. Whether and how TSLP is involved in the initial priming of T helper type-2 (Th2) differentiation against harmless antigen remains unclear. Using an intranasal sensitization protocol with OVA and LPS, we showed that TSLP signaling is required for low-dose LPS-induced Th2 inflammation, but not for high-dose LPS-induced Th1 immunity. We further demonstrated that low-dose LPS-activated bone marrow-derived dendritic cells expressed relatively high Tslp but low Il12a, and were able to prime naïve DO11.10 T cells to differentiate into Th2 cells in a TSLP-dependent manner. After transfer into wild-type recipient mice, the low-dose LPS-activated OVA-loaded dendritic cells (DCs) induced airway eosinophilia, but primed neutrophil-dominated airway inflammation when TSLP-deficient DCs were used. These studies demonstrate that TSLP released by DCs in response to a low concentration of LPS plays a role in priming Th2 differentiation and thus may serve as a polarizing third signal, in addition to antigen/MHC class II and co-stimulatory factors, from antigen-presenting DCs to direct effector T-cell differentiation.

Original languageEnglish (US)
Pages (from-to)1735-1743
Number of pages9
JournalEuropean Journal of Immunology
Volume42
Issue number7
DOIs
StatePublished - Jul 2012

Keywords

  • Allergic airway inflammation
  • Th2
  • TSLP

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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