EMBO Molecular Medicine (May 2024)
An immunohistochemical atlas of necroptotic pathway expression
- Shene Chiou,
- Aysha H Al-Ani,
- Yi Pan,
- Komal M Patel,
- Isabella Y Kong,
- Lachlan W Whitehead,
- Amanda Light,
- Samuel N Young,
- Marilou Barrios,
- Callum Sargeant,
- Pradeep Rajasekhar,
- Leah Zhu,
- Anne Hempel,
- Ann Lin,
- James A Rickard,
- Cathrine Hall,
- Pradnya Gangatirkar,
- Raymond KH Yip,
- Wayne Cawthorne,
- Annette V Jacobsen,
- Christopher R Horne,
- Katherine R Martin,
- Lisa J Ioannidis,
- Diana S Hansen,
- Jessica Day,
- Ian P Wicks,
- Charity Law,
- Matthew E Ritchie,
- Rory Bowden,
- Joanne M Hildebrand,
- Lorraine A O’Reilly,
- John Silke,
- Lisa Giulino-Roth,
- Ellen Tsui,
- Kelly L Rogers,
- Edwin D Hawkins,
- Britt Christensen,
- James M Murphy,
- André L Samson
Affiliations
- Shene Chiou
- Walter and Eliza Hall Institute of Medical Research
- Aysha H Al-Ani
- Walter and Eliza Hall Institute of Medical Research
- Yi Pan
- Walter and Eliza Hall Institute of Medical Research
- Komal M Patel
- Walter and Eliza Hall Institute of Medical Research
- Isabella Y Kong
- Pediatric Hematology/Oncology, Weill Cornell Medical College
- Lachlan W Whitehead
- Walter and Eliza Hall Institute of Medical Research
- Amanda Light
- Walter and Eliza Hall Institute of Medical Research
- Samuel N Young
- Walter and Eliza Hall Institute of Medical Research
- Marilou Barrios
- Walter and Eliza Hall Institute of Medical Research
- Callum Sargeant
- Walter and Eliza Hall Institute of Medical Research
- Pradeep Rajasekhar
- Walter and Eliza Hall Institute of Medical Research
- Leah Zhu
- Walter and Eliza Hall Institute of Medical Research
- Anne Hempel
- Walter and Eliza Hall Institute of Medical Research
- Ann Lin
- Walter and Eliza Hall Institute of Medical Research
- James A Rickard
- Walter and Eliza Hall Institute of Medical Research
- Cathrine Hall
- Walter and Eliza Hall Institute of Medical Research
- Pradnya Gangatirkar
- Walter and Eliza Hall Institute of Medical Research
- Raymond KH Yip
- Walter and Eliza Hall Institute of Medical Research
- Wayne Cawthorne
- Walter and Eliza Hall Institute of Medical Research
- Annette V Jacobsen
- Walter and Eliza Hall Institute of Medical Research
- Christopher R Horne
- Walter and Eliza Hall Institute of Medical Research
- Katherine R Martin
- Walter and Eliza Hall Institute of Medical Research
- Lisa J Ioannidis
- Walter and Eliza Hall Institute of Medical Research
- Diana S Hansen
- Walter and Eliza Hall Institute of Medical Research
- Jessica Day
- Walter and Eliza Hall Institute of Medical Research
- Ian P Wicks
- Walter and Eliza Hall Institute of Medical Research
- Charity Law
- Walter and Eliza Hall Institute of Medical Research
- Matthew E Ritchie
- Walter and Eliza Hall Institute of Medical Research
- Rory Bowden
- Walter and Eliza Hall Institute of Medical Research
- Joanne M Hildebrand
- Walter and Eliza Hall Institute of Medical Research
- Lorraine A O’Reilly
- Walter and Eliza Hall Institute of Medical Research
- John Silke
- Walter and Eliza Hall Institute of Medical Research
- Lisa Giulino-Roth
- Pediatric Hematology/Oncology, Weill Cornell Medical College
- Ellen Tsui
- Walter and Eliza Hall Institute of Medical Research
- Kelly L Rogers
- Walter and Eliza Hall Institute of Medical Research
- Edwin D Hawkins
- Walter and Eliza Hall Institute of Medical Research
- Britt Christensen
- Walter and Eliza Hall Institute of Medical Research
- James M Murphy
- Walter and Eliza Hall Institute of Medical Research
- André L Samson
- Walter and Eliza Hall Institute of Medical Research
- DOI
- https://doi.org/10.1038/s44321-024-00074-6
- Journal volume & issue
-
Vol. 16,
no. 7
pp. 1717 – 1749
Abstract
Abstract Necroptosis is a lytic form of regulated cell death reported to contribute to inflammatory diseases of the gut, skin and lung, as well as ischemic-reperfusion injuries of the kidney, heart and brain. However, precise identification of the cells and tissues that undergo necroptotic cell death in vivo has proven challenging in the absence of robust protocols for immunohistochemical detection. Here, we provide automated immunohistochemistry protocols to detect core necroptosis regulators – Caspase-8, RIPK1, RIPK3 and MLKL – in formalin-fixed mouse and human tissues. We observed surprising heterogeneity in protein expression within tissues, whereby short-lived immune barrier cells were replete with necroptotic effectors, whereas long-lived cells lacked RIPK3 or MLKL expression. Local changes in the expression of necroptotic effectors occurred in response to insults such as inflammation, dysbiosis or immune challenge, consistent with necroptosis being dysregulated in disease contexts. These methods will facilitate the precise localisation and evaluation of necroptotic signaling in vivo.
Keywords
