Dendritic Cell-Derived TSLP Negatively Regulates HIF-1α and IL-1β During Dectin-1 Signaling
Autor: | Matthew J. Elder, Steve J. Webster, Timothy J. Fitzmaurice, Aran S. D. Shaunak, Martin Steinmetz, Ronnie Chee, Ziad Mallat, E. Suzanne Cohen, David L. Williams, J. S. Hill Gaston, Jane C. Goodall |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Cell type Thymic stromal lymphopoietin medicine.medical_treatment Interleukin-1beta Immunology Syk HIF-1α 03 medical and health sciences 0302 clinical medicine medicine Immunology and Allergy Humans Lectins C-Type Autocrine signalling Original Research Effector Chemistry hypoxia ROS Dendritic cell Dendritic Cells Hypoxia-Inducible Factor 1 alpha Subunit 3. Good health Cell biology 030104 developmental biology Cytokine IL-1β TSLP Phosphorylation Cytokines dectin-1 lcsh:RC581-607 030215 immunology Signal Transduction |
Zdroj: | Frontiers in Immunology, Vol 10 (2019) Frontiers in Immunology |
ISSN: | 1664-3224 |
Popis: | Thymic stromal lymphopoietin (TSLP) is a functionally pleotropic cytokine important in immune regulation, and TSLP dysregulation is associated with numerous diseases. TSLP is produced by many cell types, but has predominantly been characterized as a secreted factor from epithelial cells which activates dendritic cells (DC) that subsequently prime T helper (TH) 2 immunity. However, DC themselves make significant amounts of TSLP in response to microbial products, but the functional role of DC-derived TSLP remains unclear. We show that TSLPR signaling negatively regulates IL-1β production during dectin-1 stimulation of human DC. This regulatory mechanism functions by dampening Syk phosphorylation and is mediated via NADPH oxidase-derived ROS, HIF-1α and pro-IL-1β expression. Considering the profound effect TSLPR signaling has on the metabolic status and the secretome of dectin-1 stimulated DC, these data suggest that autocrine TSLPR signaling could have a fundamental role in modulating immunological effector responses at sites removed from epithelial cell production of TSLP. |
Databáze: | OpenAIRE |
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