TSLP production by dendritic cells is modulated by IL-1β and components of the endoplasmic reticulum stress response
European Journal of Immunology
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Elder, M. J., Webster, S., Williams, D. L., Gaston, H., & Goodall, J. (2015). TSLP production by dendritic cells is modulated by IL-1β and components of the endoplasmic reticulum stress response. European Journal of Immunology, 46 455-463. https://doi.org/10.1002/eji.201545537
Thymic stromal lymphopoietin (TSLP) produced by epithelial cells acts on dendritic cells (DCs) to drive differentiation of TH2-cells, and is therefore important in allergic disease pathogenesis. However, DCs themselves make significant amounts of TSLP in response to microbial products, but little is known about the key downstream signals that induce and modulate this TSLP secretion from human DCs. We show that human monocyte derived DC (mDC) secretion of TSLP in response to Candida albicans and β-glucans requires dectin-1, Syk, NF-κB, and p38 MAPK signaling. In addition, TSLP production by mDCs is greatly enhanced by IL-1β, but not TNF-α, in contrast to epithelial cells. Furthermore, TSLP secretion is significantly increased by signals emanating from the endoplasmic reticulum (ER) stress response, specifically the unfolded protein response sensors, inositol-requiring transmembrane kinase/endonuclease 1 and protein kinase R-like ER kinase, which are activated by dectin-1 stimulation. Thus, TSLP production by mDCs requires the integration of signals from dectin-1, the IL-1 receptor, and ER stress signaling pathways. Autocrine TSLP production is likely to play a role in mDC-controlled immune responses at sites removed from epithelial cell production of the cytokine, such as lymphoid tissue.
dectin-1, ER stress, IL-1β, TSLP
This research was supported by Arthritis Research UK and the Cambridge NIHR BRC Cell Phenotyping Hub. This research was also supported, in part, by NIH GM53522 and GM083016 to D.L.W.
Arthritis Research Uk (19639)
Arthritis Research Uk (19962)
External DOI: https://doi.org/10.1002/eji.201545537
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253252
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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