Inflammasome-Dependent Induction of Adaptive NK Cell Memory.
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.
Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany. Electronic address: jvdboorn@uni-bonn.de.
Jasper G
JG
van den Boorn
Institute of Molecular Medicine, University Hospital Bonn, Bonn, Germany.
Christopher
C
Jakobs
Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Christian
C
Hagen
Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Marcel
M
Renn
Department for Dermatology and Netherlands Institute for Pigment Disorders, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Rosalie M
RM
Luiten
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands; ISA Pharmaceuticals, Leiden, the Netherlands.
Cornelis J M
CJ
Melief
Department for Dermatology and Allergy, University Hospital Bonn, Bonn, Germany.
Thomas
T
Tüting
Institute of Experimental Immunology, University Hospital Bonn, Bonn, Germany.
Natalio
N
Garbi
Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Gunther
G
Hartmann
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.
Veit
V
Hornung
D056704:Adaptive Immunity; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D053468:CARD Signaling Adaptor Proteins; D002478:Cells, Cultured; D003877:Dermatitis, Contact / Q000276:immunology*; D006873:Hydroquinones; D007156:Immunologic Memory; D058847:Inflammasomes / Q000276:immunology*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000473:pathology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000502:physiology*; D008544:Melanocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D006873:Hydroquinones; D058847:Inflammasomes; D020382:Interleukin-18; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C498534:Pycard protein, mouse; C006429:monobenzone