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Immunity. 2016 Jun 21;44(6):1406-21. doi: 10.1016/j.immuni.2016.05.008. Epub 2016 Jun 7.

Inflammasome-Dependent Induction of Adaptive NK Cell Memory.

Author information

1
Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany. Electronic address: jvdboorn@uni-bonn.de.
2
Institute of Molecular Medicine, University Hospital Bonn, Bonn, Germany.
3
Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
4
Department for Dermatology and Netherlands Institute for Pigment Disorders, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
5
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands; ISA Pharmaceuticals, Leiden, the Netherlands.
6
Department for Dermatology and Allergy, University Hospital Bonn, Bonn, Germany.
7
Institute of Experimental Immunology, University Hospital Bonn, Bonn, Germany.
8
Institute of Molecular Medicine, University Hospital Bonn, Bonn, Germany; Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany. Electronic address: hornung@genzentrum.lmu.de.

Abstract

Monobenzone is a pro-hapten that is exclusively metabolized by melanocytes, thereby haptenizing melanocyte-specific antigens, which results in cytotoxic autoimmunity specifically against pigmented cells. Studying monobenzone in a setting of contact hypersensitivity (CHS), we observed that monobenzone induced a long-lasting, melanocyte-specific immune response that was dependent on NK cells, yet fully intact in the absence of T- and B cells. Consistent with the concept of "memory NK cells," monobenzone-induced NK cells resided in the liver and transfer of these cells conferred melanocyte-specific immunity to naive animals. Monobenzone-exposed skin displayed macrophage infiltration and cutaneous lymph nodes showed an inflammasome-dependent influx of macrophages with a tissue-resident phenotype, coinciding with local NK cell activation. Indeed, macrophage depletion or the absence of the NLRP3 inflammasome, the adaptor protein ASC or interleukin-18 (IL-18) abolished monobenzone CHS, thereby establishing a non-redundant role for the NLRP3 inflammasome as a critical proinflammatory checkpoint in the induction of hapten-dependent memory NK cells.

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PMID:
27287410
DOI:
10.1016/j.immuni.2016.05.008
[Indexed for MEDLINE]
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