Induced Pluripotent Stem Cell-derived Monocytic Cell Lines from a NOMID Patient Serve As a Screening Platform for Modulating NLRP3 Inflammasome Activity

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2020 Aug 19

PMID 32810141

Citations 8

Authors

Ryosuke Seki

Akira Ohta

Akira Niwa

Yoshinori Sugimine

Haruna Naito

Tatsutoshi Nakahata

Megumu K Saito

Affiliations

Soon will be listed here.

Abstract

Curative therapeutic options for a number of immunological disorders remain to be established, and approaches for identifying drug candidates are relatively limited. Furthermore, phenotypic screening methods using induced pluripotent stem cell (iPSC)-derived immune cells or hematopoietic cells need improvement. In the present study, using immortalized monocytic cell lines derived from iPSCs, we developed a high-throughput screening (HTS) system to detect compounds that inhibit IL-1β secretion and NLRP3 inflammasome activation from activated macrophages. The iPSCs were generated from a patient with neonatal onset multisystem inflammatory disease (NOMID) as a model of a constitutively activated NLRP3 inflammasome. HTS of 4,825 compounds including FDA-approved drugs and compounds with known bioactivity identified 7 compounds as predominantly IL-1β inhibitors. Since these compounds are known inflammasome inhibitors or derivatives of, these results prove the validity of our HTS system, which can be a versatile platform for identifying drug candidates for immunological disorders associated with monocytic lineage cells.

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