Journal article
Autoinflammatory mutation in NLRC4 reveals a leucine-rich repeat (LRR)–LRR oligomerization interface
F Moghaddas, P Zeng, Y Zhang, H Schützle, S Brenner, SR Hofmann, R Berner, Y Zhao, B Lu, X Chen, L Zhang, S Cheng, S Winkler, K Lehmberg, SW Canna, PE Czabotar, IP Wicks, D De Nardo, CM Hedrich, H Zeng Show all
Journal of Allergy and Clinical Immunology | MOSBY-ELSEVIER | Published : 2018
Abstract
Background: Monogenic autoinflammatory disorders are characterized by dysregulation of the innate immune system, for example by gain-of-function mutations in inflammasome-forming proteins, such as NOD-like receptor family CARD-containing 4 protein (NLRC4). Objective: Here we investigate the mechanism by which a novel mutation in the leucine-rich repeat (LRR) domain of NLRC4 (c.G1965C, p.W655C) contributes to autoinflammatory disease. Methods: We studied 2 unrelated patients with early-onset macrophage activation syndrome harboring the same de novo mutation in NLRC4. In vitro inflammasome complex formation was quantified by using flow cytometric analysis of apoptosis-associated speck-like pro..
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Awarded by School of Medicine, University of North Carolina at Chapel Hill
Funding Acknowledgements
Funding for this work was provided by a Australian National Health and Medical Research Council Program (NHMRC) project grant (1113577; to I.P.W.); NHMRC projects grants (1099262 and 1081299), a Viertel Fellowship, the Howard Hughes Medical Institute, and GlaxoSmithKline (to S.L.M.); the National Natural Science Foundation of China (31770978) and Children's Medical Centre Startup Fund (5001-3001032; to Y.Z.); the intramural MeDDrive program of TU Dresden and the Fritz-Thyssen Foundation (to C.M.H.); internal funding of the Paediatric Institute of Guangzu and a Guangzhou Women and Children's Medical Centre project grant (0160001; to P.Z.); and the German Research Foundation (KF0249, HO4510/1-2; to S.R.H.).