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Cell Rep. 2016 Sep 20;16(12):3273-3285. doi: 10.1016/j.celrep.2016.08.061.

Human iNKT Cells Promote Protective Inflammation by Inducing Oscillating Purinergic Signaling in Monocyte-Derived DCs.

Author information

1
Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
2
Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
3
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
4
Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
5
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
6
Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA. Electronic address: jegumperz@wisc.edu.

Abstract

Invariant natural killer T (iNKT) cells are innate T lymphocytes that promote host defense against a variety of microbial pathogens. Whether microbial ligands are required for their protective effects remains unclear. Here, we show that iNKT cells stimulate human-monocyte-derived dendritic cells (DCs) to produce inflammatory mediators in a manner that does not require the presence of microbial compounds. Interleukin 2 (IL-2)-exposed iNKT cells selectively induced repeated cytoplasmic Ca(2+) fluxes in DCs that were dependent on signaling by the P2X7 purinergic receptor and mediated by ATP released during iNKT-DC interactions. Exposure to iNKT cells led to DC cyclooxygenase 2 (PTGS2) gene transcription, and release of PGE2 that was associated with vascular permeabilization in vivo. Additionally, soluble factors were released that induced neutrophil recruitment and activation and enhanced control of Candida albicans. These results suggest that sterile interactions between iNKT cells and monocyte-derived DCs lead to the production of non-redundant inflammatory mediators that promote neutrophil responses.

PMID:
27653689
PMCID:
PMC5043518
DOI:
10.1016/j.celrep.2016.08.061
[Indexed for MEDLINE]
Free PMC Article

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