Inflammasome-Dependent Induction of Adaptive NK Cell Memory

Boorn, Jasper G. van den; Jakobs, Christopher; Hagen, Christian; Renn, Marcel; Luiten, Rosalie M.; Melief, Cornelis J. M.; Tüting, Thomas; Garbi, Natalio; Hartmann, Gunther and Hornung, Veit (2016): Inflammasome-Dependent Induction of Adaptive NK Cell Memory. In: Immunity, Vol. 44, No. 6: pp. 1406-1421

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," mono-benzone- 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.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Biochemistry
• Subjects: 500 Science > 540 Chemistry
• ISSN: 1074-7613
• Language: English