Inflammasome-Dependent Induction of Adaptive NK Cell Memory.

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.

• Authors: Jasper G van den Boorn, Christopher Jakobs, Christian Hagen, Marcel Renn, Rosalie M Luiten, Cornelis J M Melief, Thomas Tüting, Natalio Garbi, Gunther Hartmann, Veit Hornung
• Journal: Immunity (Immunity) Vol. 44 Issue 6 Pg. 1406-21 (06 21 2016) ISSN: 1097-4180 [Electronic] United States
• PMID: 27287410 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Apoptosis Regulatory Proteins
• CARD Signaling Adaptor Proteins
• Hydroquinones
• Inflammasomes
• Interleukin-18
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Pycard protein, mouse
• monobenzone

Topics

• Adaptive Immunity
• Animals
• Apoptosis Regulatory Proteins (genetics, metabolism)
• CARD Signaling Adaptor Proteins
• Cells, Cultured
• Dermatitis, Contact (immunology)
• Hydroquinones
• Immunologic Memory
• Inflammasomes (immunology)
• Interleukin-18 (genetics, metabolism)
• Killer Cells, Natural (immunology)
• Liver (pathology)
• Lymphocyte Activation
• Macrophages (physiology)
• Melanocytes (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)