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TSLP production by dendritic cells is modulated by IL-1β and components of the endoplasmic reticulum stress response.
Eur J Immunol 2016; 46(2):455-63EJ

Abstract

Thymic stromal lymphopoietin (TSLP) produced by epithelial cells acts on dendritic cells (DCs) to drive differentiation of TH 2-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.

Authors+Show Affiliations

Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrookes Hospital, Cambridge, UK.Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrookes Hospital, Cambridge, UK.Department of Surgery, Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrookes Hospital, Cambridge, UK.Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrookes Hospital, Cambridge, UK.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26573878

Citation

Elder, Matthew J., et al. "TSLP Production By Dendritic Cells Is Modulated By IL-1β and Components of the Endoplasmic Reticulum Stress Response." European Journal of Immunology, vol. 46, no. 2, 2016, pp. 455-63.
Elder MJ, Webster SJ, Williams DL, et al. TSLP production by dendritic cells is modulated by IL-1β and components of the endoplasmic reticulum stress response. Eur J Immunol. 2016;46(2):455-63.
Elder, M. J., Webster, S. J., Williams, D. L., Gaston, J. S., & Goodall, J. C. (2016). TSLP production by dendritic cells is modulated by IL-1β and components of the endoplasmic reticulum stress response. European Journal of Immunology, 46(2), pp. 455-63. doi:10.1002/eji.201545537.
Elder MJ, et al. TSLP Production By Dendritic Cells Is Modulated By IL-1β and Components of the Endoplasmic Reticulum Stress Response. Eur J Immunol. 2016;46(2):455-63. PubMed PMID: 26573878.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TSLP production by dendritic cells is modulated by IL-1β and components of the endoplasmic reticulum stress response. AU - Elder,Matthew J, AU - Webster,Steven J, AU - Williams,David L, AU - Gaston,J S Hill, AU - Goodall,Jane C, Y1 - 2015/12/02/ PY - 2015/01/30/received PY - 2015/10/02/revised PY - 2015/11/09/accepted PY - 2015/11/18/entrez PY - 2015/11/18/pubmed PY - 2016/7/1/medline KW - Dectin-1 KW - ER stress KW - IL-1β KW - TSLP SP - 455 EP - 63 JF - European journal of immunology JO - Eur. J. Immunol. VL - 46 IS - 2 N2 - Thymic stromal lymphopoietin (TSLP) produced by epithelial cells acts on dendritic cells (DCs) to drive differentiation of TH 2-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. SN - 1521-4141 UR - https://www.unboundmedicine.com/medline/citation/26573878/TSLP_production_by_dendritic_cells_is_modulated_by_IL_1β_and_components_of_the_endoplasmic_reticulum_stress_response_ L2 - https://doi.org/10.1002/eji.201545537 DB - PRIME DP - Unbound Medicine ER -