An immunohistochemical atlas of necroptotic pathway expression

Chiou, S; Al-Ani, AH; Pan, Y; Patel, KM; Kong, IY; Whitehead, LW; Light, A; Young, SN; Barrios, M; Sargeant, C; Rajasekhar, P; Zhu, L; Hempel, A; Lin, A; Rickard, JA; Hall, C; Gangatirkar, P; Yip, RK; Cawthorne, W; Jacobsen, AV; Horne, CR; Martin, KR; Ioannidis, LJ; Hansen, DS; Day, J; Wicks, IP; Law, C; Ritchie, ME; Bowden, R; Hildebrand, JM; O&#39;Reilly, LA; Silke, J; Giulino-Roth, L; Tsui, E; Rogers, KL; Hawkins, ED; Christensen, B; Murphy, JM; Samson, AL

Author(s): Chiou, S; Al-Ani, AH; Pan, Y; Patel, KM; Kong, IY; Whitehead, LW; Light, A; Young, SN; Barrios, M; Sargeant, C; Rajasekhar, P; Zhu, L; Hempel, A; Lin, A; Rickard, JA; Hall, C; Gangatirkar, P; Yip, RK; Cawthorne, W; Jacobsen, AV; Horne, CR; Martin, KR; Ioannidis, LJ; Hansen, DS; Day, J; Wicks, IP; Law, C; Ritchie, ME; Bowden, R; Hildebrand, JM; O'Reilly, LA; Silke, J; Giulino-Roth, L; Tsui, E; Rogers, KL; Hawkins, ED; Christensen, B; Murphy, JM; Samson, AL;
Details: Publication Year 2024-05-15,Volume 16,Issue #7,Page 1717-1749
Journal Title: EMBO Molecular Medicine
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.
Publisher: EMBO Press
Keywords: Ibd; Immunohistochemistry; Mlkl; Necroptosis; Ripk3
Research Division(s): Inflammation; Advanced Technology And Biology; Advanced Technology and Biology
PubMed ID: 38750308
Publisher's Version: https://doi.org/10.1038/s44321-024-00074-6
Open Access at Publisher's Site: https://doi.org/ 10.1038/s44321-024-00074-6
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-05-20 07:53:34

Last Modified: 2024-07-26 09:30:23