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Dectin-1 Controls TSLP-Induced Th2 Response by Regulating STAT3, STAT6, and p50-RelB Activities in Dendritic Cells.
- Source :
-
Frontiers in immunology [Front Immunol] 2021 Jul 07; Vol. 12, pp. 678036. Date of Electronic Publication: 2021 Jul 07 (Print Publication: 2021). - Publication Year :
- 2021
-
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.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Gu, Upchurch, Horton, Wiest, Zurawski, Millard, Kane, Joo, Miller and Oh.)
- Subjects :
- Adult
Allergens administration & dosage
Allergens immunology
Animals
Antigens, Dermatophagoides administration & dosage
Antigens, Dermatophagoides immunology
Antigens, Plant pharmacology
Case-Control Studies
Dermatophagoides farinae immunology
Disease Models, Animal
Female
HEK293 Cells
Humans
Hypersensitivity blood
Lectins, C-Type agonists
Macaca mulatta
Male
Middle Aged
OX40 Ligand metabolism
Plant Proteins pharmacology
Th2 Cells drug effects
beta-Glucans pharmacology
Thymic Stromal Lymphopoietin
Cytokines pharmacology
Dendritic Cells immunology
Hypersensitivity immunology
Immunity drug effects
Lectins, C-Type metabolism
NF-kappa B p50 Subunit metabolism
STAT3 Transcription Factor metabolism
STAT6 Transcription Factor metabolism
Signal Transduction drug effects
Th2 Cells immunology
Transcription Factor RelB metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34305908
- Full Text :
- https://doi.org/10.3389/fimmu.2021.678036