Dendritic Cell-Derived TSLP Negatively Regulates HIF-1α and IL-1β During Dectin-1 Signaling
Year: 2019
Type: article
Abstract: 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 characterised 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 signalling 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 signalling has on the metabolic status and the secretome of dectin-1 stimulated DC, these data suggest that autocrine TSLPR signalling could have a fundamental role in modulating immunological effector responses at sites removed from epithelial cell production of TSLP.
Source: Frontiers in Immunology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Awards: G1255693949, Amelioration of Sepsis by Macrophage Activation, BHF Chair of Cardiovascular Medicine, Training Innate Immunity: A new approach to the treatment of Sepsis, A dynamic insight into the interaction of Chlamydia trachomatis with host cells, G5845234914, Clinical/Translational Facilities for Innovative Oral Health Research at UIC, Defining the role(s) of selective subsets of antigen presenting cells in promoting or preventing atherosclerosis. (Renewal), G8454929189, Innate Immunity and Cardiovascular Function in Sepsis
OpenAlex ID: W2944465292