Laquinimod, a prototypic quinoline-3-carboxamide and aryl hydrocarbon receptor agonist, utilizes a CD155-mediated natural killer/dendritic cell interaction to suppress CNS autoimmunity

Journal of Neuroinflammation
Martina OttStefan Nessler

Abstract

Quinoline-3-carboxamides, such as laquinimod, ameliorate CNS autoimmunity in patients and reduce tumor cell metastasis experimentally. Previous studies have focused on the immunomodulatory effect of laquinimod on myeloid cells. The data contained herein suggest that quinoline-3-carboxamides improve the immunomodulatory and anti-tumor effects of NK cells by upregulating the adhesion molecule DNAX accessory molecule-1 (DNAM-1). We explored how NK cell activation by laquinimod inhibits CNS autoimmunity in experimental autoimmune encephalomyelitis (EAE), the most utilized model of MS, and improves immunosurveillance of experimental lung melanoma metastasis. Functional manipulations included in vivo NK and DC depletion experiments and in vitro assays of NK cell function. Clinical, histological, and flow cytometric read-outs were assessed. We demonstrate that laquinimod activates natural killer (NK) cells via the aryl hydrocarbon receptor and increases their DNAM-1 cell surface expression. This activation improves the cytotoxicity of NK cells against B16F10 melanoma cells and augments their immunoregulatory functions in EAE by interacting with CD155+ dendritic cells (DC). Noteworthy, the immunosuppressive effect of laquinimod-activat...Continue Reading

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Citations

Aug 21, 2020·Expert Opinion on Investigational Drugs·Fanni Boros, László Vécsei
Feb 23, 2020·Journal of Neuroinflammation·Kaili LuYuwu Zhao
Jan 8, 2021·Neurology. Neuroimmunology and Neuroinflammation·Veit RothhammerFrancisco J Quintana
Jan 10, 2021·Journal of Reproductive Immunology·Shao-Liang YangMing-Qing Li
Aug 27, 2021·Journal of Experimental & Clinical Cancer Research : CR·Baokang WuYu Tian

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Methods Mentioned

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flow cytometry
ELISA
dissection

Software Mentioned

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