Dectin-1 Controls TSLP-Induced Th2 Response by Regulating STAT3, STAT6, and p50-RelB Activities in Dendritic Cells
| Autor: | Gu, Chao, Upchurch, Katherine, Horton, Joshua, Wiest, Mathew, Zurawski, Sandra, Millard, Mark, Kane, Robert R, Joo, HyeMee, Miller, Lisa A, Oh, SangKon |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
STAT3 Transcription Factor Male beta-Glucans Immunology OX40 Ligand Vaccine Related STAT3 Th2 Cells Thymic Stromal Lymphopoietin Clinical Research Biodefense Lectins Hypersensitivity Dermatophagoides Animals Humans 2.1 Biological and endogenous factors dendritic cells Antigens Aetiology Plant Proteins STAT6 Dermatophagoides farinae C-Type Animal Prevention Inflammatory and immune system Transcription Factor RelB Immunity NF-kappa B p50 Subunit Plant Allergens Middle Aged allergy Macaca mulatta OX40L HEK293 Cells Emerging Infectious Diseases Medical Microbiology Case-Control Studies TSLP Disease Models Cytokines Female STAT6 Transcription Factor Dectin-1 Signal Transduction |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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