2026-06-14T03:46:50Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/204632024-11-28T20:11:12Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Lee, Pamela P author Lobato-Marquez, Damian author Pramanik, Nayani author Sirianni, Andrea author Daza-Cajigal, Vanessa author Rivers, Elizabeth author Cavazza, Alessia author Bouma, Gerben author Moulding, Dale author Hultenby, Kjell author Westerberg, Lisa S author Hollinshead, Michael author Lau, Yu-Lung author Burns, Siobhan O author Mostowy, Serge author Bajaj-Elliott, Mona author Thrasher, Adrian J author 2017-11-17 Dysregulation of autophagy and inflammasome activity contributes to the development of auto-inflammatory diseases. Emerging evidence highlights the importance of the actin cytoskeleton in modulating inflammatory responses. Here we show that deficiency of Wiskott-Aldrich syndrome protein (WASp), which signals to the actin cytoskeleton, modulates autophagy and inflammasome function. In a model of sterile inflammation utilizing TLR4 ligation followed by ATP or nigericin treatment, inflammasome activation is enhanced in monocytes from WAS patients and in WAS-knockout mouse dendritic cells. In ex vivo models of enteropathogenic Escherichia coli and Shigella flexneri infection, WASp deficiency causes defective bacterial clearance, excessive inflammasome activation and host cell death that are associated with dysregulated septin cage-like formation, impaired autophagic p62/LC3 recruitment and defective formation of canonical autophagosomes. Taken together, we propose that dysregulation of autophagy and inflammasome activities contribute to the autoinflammatory manifestations of WAS, thereby identifying potential targets for therapeutic intervention. Lee Pamela P, Lobato-Marquez D, Pramanik N, Sirianni A, Daza Cajigal VC, Rivers E, et al. Wiskott-Aldrich syndrome protein regulates autophagy and inflammasome activity in innate immune cells. Nat Commun. 2017 Nov 17;8:1576. 10.1038/s41467-017-01676-0 2041-1723 Nature Communications http://hdl.handle.net/20.500.13003/9556 29146903 L619287601 2-s2.0-85034614435 http://hdl.handle.net/20.500.12105/20463 415648900008 Wiskott-Aldrich syndrome protein regulates autophagy and inflammasome activity in innate immune cells