@article{904efbb2b36b49d5b3f150dc3eb4744e,
title = "NAIP-NLRC4 Inflammasomes Coordinate Intestinal Epithelial Cell Expulsion with Eicosanoid and IL-18 Release via Activation of Caspase-1 and -8",
abstract = "Intestinal epithelial cells (IECs) form a critical barrier against pathogen invasion. By generation of mice in which inflammasome expression is restricted to IECs, we describe a coordinated epithelium-intrinsic inflammasome response in vivo. This response was sufficient to protect against Salmonella tissue invasion and involved a previously reported IEC expulsion that was coordinated with lipid mediator and cytokine production and lytic IEC death. Excessive inflammasome activation in IECs was sufficient to result in diarrhea and pathology. Experiments with IEC organoids demonstrated that IEC expulsion did not require other cell types. IEC expulsion was accompanied by a major actin rearrangement in neighboring cells that maintained epithelium integrity but did not absolutely require Caspase-1 or Gasdermin D. Analysis of Casp1–/–Casp8–/– mice revealed a functional Caspase-8 inflammasome in vivo. Thus, a coordinated IEC-intrinsic, Caspase-1 and -8 inflammasome response plays a key role in intestinal immune defense and pathology.",
keywords = "ASC, Caspase-1, Caspase-8, Naip, Nlrc4, expulsion, extrusion, inflammasome, intestinal epithelial cell",
author = "Isabella Rauch and Deets, {Katherine A.} and Ji, {Daisy X.} and {von Moltke}, Jakob and Tenthorey, {Jeannette L.} and Lee, {Angus Y.} and Philip, {Naomi H.} and Ayres, {Janelle S.} and Brodsky, {Igor E.} and Karsten Gronert and Vance, {Russell E.}",
note = "Funding Information: We acknowledge the assistance of the UC Berkeley CRL Flow Cytometry Laboratory, Eric Chen, Peter Dietzen, Roberto Chavez, Jake Wu, and James Kang for technical support, the Vance and Barton Labs for discussions, and Greg Barton for comments on the manuscript. We thank Xiaodong Wang for Ripk3–/– mice and the Winoto Lab for backcrossing the mice to the C57BL/6 background. This work was supported by HHMI and NIH grants to R.E.V. (AI075039, AI063302) and NIH grant (EY026082) to K.G. R.E.V. was a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease and is an Investigator of the Howard Hughes Medical Institute. Research reported in this publication was supported in part by the NIH S10 program under award number 1S10RR026866-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. I.R. is supported by the Austrian Science Fund (FWF) (the Erwin Schr{\"o}dinger Fellowship J3789-B22). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = apr,
day = "18",
doi = "10.1016/j.immuni.2017.03.016",
language = "English (US)",
volume = "46",
pages = "649--659",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "4",
}