@article{a9b98c92e1ee486a964b7c5258b8478b,
title = "An immunohistochemical atlas of necroptotic pathway expression",
abstract = "(Figure presented.) Necroptotic cell death is broadly linked to inflammation-associated diseases such as IBD. But, accurately identifying when and where necroptosis occurs in human disease has proven difficult. Using new methods to detect the key regulators of necroptosis - Caspase-8, RIPK1, RIPK3, MLKL - we find that: Expression of the necroptotic pathway is rare under basal conditions and largely restricted to fast-cycling barrier cells such as the intestinal epithelium. RIPK3 is a novel acute phase reactant, with levels that rapidly change in response to physiological challenges including inflammation, dysbiosis and immunisation. Exaggerated necroptosis arises in a subset of IBD patients. Subcellular relocation of Caspase-8 and other key regulators is a clinically relevant approach to pinpoint necroptosis in mouse and human tissues.",
keywords = "IBD, Immunohistochemistry, MLKL, Necroptosis, RIPK3",
author = "Shene Chiou and Al-Ani, {Aysha H.} and Yi Pan and Patel, {Komal M.} and Kong, {Isabella Y.} and Whitehead, {Lachlan W.} and Amanda Light and Young, {Samuel N.} and Marilou Barrios and Callum Sargeant and Pradeep Rajasekhar and Leah Zhu and Anne Hempel and Ann Lin and Rickard, {James A.} and Cathrine Hall and Pradnya Gangatirkar and Yip, {Raymond K.H.} and Wayne Cawthorne and Jacobsen, {Annette V.} and Horne, {Christopher R.} and Martin, {Katherine R.} and Ioannidis, {Lisa J.} and Hansen, {Diana S.} and Jessica Day and Wicks, {Ian P.} and Charity Law and Ritchie, {Matthew E.} and Rory Bowden and Hildebrand, {Joanne M.} and O{\textquoteright}Reilly, {Lorraine A.} and John Silke and Lisa Giulino-Roth and Ellen Tsui and Rogers, {Kelly L.} and Hawkins, {Edwin D.} and Britt Christensen and Murphy, {James M.} and Samson, {Andr{\'e} L.}",
note = "Funding Information: We thank James Vince, Jiyi Pang, David Tarlington, Angus Stock, Najoua Lalaoui, Asha Jois, Marcel Doerflinger, Quentin Gouil, Eric Hanssen, Phil Arandjelovic, Imadh Azeez and Bruce Rosengarten for constructive feedback and/or reagents during the preparation of this manuscript. We thank WEHI Monoclonal antibody facility for producing several antibodies used in this study. We thank the WEHI Histology team for high-level support with immunohistochemistry. We thank the WEHI Bioservices team for high-level support for animal experimentation, welfare, and ethics. We thank Kim Newton and Vishva Dixit for sharing the Ripk3 mice that were used to make the Casp8Ripk3 mice, and thank Michelle Kelliher for the Ripk1 mice that were used to generate the Casp8Ripk1Ripk3 mice. We thank Anaxis Pharma Pty Ltd for providing human RIPK3 expressing mice for our control experiments, and thank Andrew Kueh and Ueli Nachbur for their roles in generating this strain. We are grateful to the Department of Gastroenterology at the Royal Melbourne Hospital for performing endoscopies and to the patients who consented to donating their material to be used in this study. This work was supported by the National Health and Medical Research Council of Australia (grants 1172929 to JMM, 2008652 to EDH, 2002965 to ALS, and the Independent Research Institutes Infrastructure Support Scheme 9000719), by the Kenneth Rainin Foundation (award to JMM, BC, AHA, ALS), and by the Victorian State Government Operational Infrastructure Support scheme. SC is supported by the WEHI Handman PhD scholarship, and AHA by the Avant Foundation, Crohn\u2019s and Colitis Australia, and the University of Melbourne Scholarships. JMM and JS received research funding from Anaxis Pharma Pty Ltd, from which the salaries of KMP, AH, AL, and PG were paid. Publisher Copyright: {\textcopyright} The Author(s) 2024.",
year = "2024",
doi = "10.1038/s44321-024-00074-6",
language = "English",
journal = "EMBO Molecular Medicine",
issn = "1757-4684",
publisher = "EMBO Press",
}
