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首页|TNFR2 induced priming of NLRP3-inflammasome via RIPK1 leads to pyroptosis in XIAP deficient cells
10.1101/550749
来源：bioRxiv_logobioRxiv

TNFR2 induced priming of NLRP3-inflammasome via RIPK1 leads to pyroptosis in XIAP deficient cells

TNFR2 induced priming of NLRP3-inflammasome via RIPK1 leads to pyroptosis in XIAP deficient cells

Robinson Mark D. 1Kaufmann Thomas 2Wong W. Wei-Lynn 3Yabal Monica 4Jost Philipp J. 4Wajant Harald 5Knop Janin 3Rufli Stefanie 3Vasilikos Lazaros 3Reinhart Ramona 2Spilgies Lisanne M.3

1. Institute of Molecular Life Sciences and SIB Swiss Institute of Bioinformatics, University of Z¨1rich 2. Institute of Pharmacology, University of Bern 3. Institute of Experimental Immunology, University of Z¨1rich 4. III. Medizinische Klink, Klinikum rechts der Isar, Technische Universit?t M¨1nchen 5. Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital W¨1rzburg

基础医学生物科学研究方法、生物科学研究技术分子生物学

Robinson Mark D.,Kaufmann Thomas,Wong W. Wei-Lynn,Yabal Monica,Jost Philipp J.,Wajant Harald,Knop Janin,Rufli Stefanie,Vasilikos Lazaros,Reinhart Ramona,Spilgies Lisanne M..TNFR2 induced priming of NLRP3-inflammasome via RIPK1 leads to pyroptosis in XIAP deficient cells[EB/OL].(2025-03-28)[2025-10-27].https://www.biorxiv.org/content/10.1101/550749.点此复制

Summary Recent data suggests that LPS stimulation can trigger inflammasome activation through a TNFR2/TNF/TNFR1 mediated loop in xiap?/? macrophages. Yet, the direct role TNFR2-specific activation plays in the absence of XIAP is unknown. We found TNFR2-specific activation lead to cell death in xiap?/? myeloid cells, particularly in the absence the RING domain. RIPK1/TAK1 kinase activity downstream of TNFR2 resulted in a TNF/TNFR1 cell death independent of necroptosis. TNFR2-specific activation lead to a similar inflammatory NF-kB driven transcriptional profile as TNFR1 activation with the exception of up-regulation of NLRP3 and caspase-11. Activation and up-regulation of the canonical inflammasome was mediated by RIPK1 kinase activity and ROS production. While both RIPK1 kinase activity and ROS production reduced cell death as well as release of IL-1β, the release of IL-18 was not reduced to basal levels. This study supports, targeting TNFR2 specifically to reduce IL-18 release in XIAP deficient (XLP-2) patients.

XLP-2XIAPTNFR2RIPK1ROSinflammasomeTNFNLRP3gasdermin DIL-18

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