Dectin-1 Controls TSLP-Induced Th2 Response by Regulating STAT3, STAT6, and p50-RelB Activities in Dendritic Cells

Chao Gu, Katherine Upchurch, Joshua Horton, Mathew Wiest, Sandra Zurawski, Mark Millard, Robert R. Kane, Hye Mee Joo, Lisa A. Miller, Sang Kon Oh

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The epithelium-associated cytokine thymic stromal lymphopoietin (TSLP) can induce OX40L and CCL17 expression by myeloid dendritic cells (mDCs), which contributes to aberrant Th2-type immune responses. Herein, we report that such TSLP-induced Th2-type immune response can be effectively controlled by Dectin-1, a C-type lectin receptor expressed by mDCs. Dectin-1 stimulation induced STAT3 activation and decreased the transcriptional activity of p50-RelB, both of which resulted in reduced OX40L expression on TSLP-activated mDCs. Dectin-1 stimulation also suppressed TSLP-induced STAT6 activation, resulting in decreased expression of the Th2 chemoattractant CCL17. We further demonstrated that Dectin-1 activation was capable of suppressing ragweed allergen (Amb a 1)-specific Th2-type T cell response in allergy patients ex vivo and house dust mite allergen (Der p 1)-specific IgE response in non-human primates in vivo. Collectively, this study provides a molecular explanation of Dectin-1-mediated suppression of Th2-type inflammatory responses and suggests Dectin-1 as a target for controlling Th2-type inflammation.

Original languageEnglish (US)
Article number678036
JournalFrontiers in immunology
Volume12
DOIs
StatePublished - Jul 7 2021
Externally publishedYes

Keywords

  • allergy
  • Dectin-1
  • dendritic cells
  • OX40L
  • STAT3
  • STAT6
  • Th2 cells
  • TSLP

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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