Document Type
Article
Publication Date
2-1-2016
Description
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Citation Information
Elder, Matthew J.; Webster, Steven J.; Williams, David L.; Gaston, J. S.Hill; and Goodall, Jane C.. 2016. Tslp Production by Dendritic Cells Is Modulated by IL-1β and Components of the Endoplasmic Reticulum Stress Response. European Journal of Immunology. Vol.46(2). 455-463. https://doi.org/10.1002/eji.201545537 PMID: 26573878 ISSN: 0014-2980
Copyright Statement
C 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.