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

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. Copyright © 2021 Gu, Upchurch, Horton, Wiest, Zurawski, Millard, Kane, Joo, Miller and Oh.

Citation

Chao Gu, Katherine Upchurch, Joshua Horton, Mathew Wiest, Sandra Zurawski, Mark Millard, Robert R Kane, HyeMee Joo, Lisa A Miller, SangKon Oh. Dectin-1 Controls TSLP-Induced Th2 Response by Regulating STAT3, STAT6, and p50-RelB Activities in Dendritic Cells. Frontiers in immunology. 2021;12:678036

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PMID: 34305908

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