NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions
Open accessAbstract
Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation of nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon. Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-κB-independent functions. Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency. Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.
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NEMO prevents RIPK1-driven intestinal inflammation and epithelial cell death, although underlying mechanisms remain poorly understood.
“Inhibitor of nuclear factor kappa B kinase subunit gamma (IKBKG; best known as NEMO) also prevents RIPK1-driven intestinal inflammation and epithelial cell death, although the underlying molecular mechanisms remain poorly understood [511]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [511]
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Cites
Interactions Between the Microbiota and the Immune System
Hooper, L. V., Littman, D. R., & Macpherson, A. J. (2012) · Science · doi:10.1126/science.1223490 · Cited by 4,173 · see citing works
NF-κB: linking inflammation and immunity to cancer development and progression
Karin, M., & Greten, F. R. (2005) · Nature reviews. Immunology · doi:10.1038/nri1703 · Cited by 3,091 · see citing works
The NF- B Family of Transcription Factors and Its RegulationPreprint
Oeckinghaus, A., & Ghosh, S. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000034 · Cited by 2,850 · see citing works
Necroptosis and its role in inflammation
Pasparakis, M., & Vandenabeele, P. (2015) · Nature · doi:10.1038/nature14191 · Cited by 2,148 · see citing works
Self-citationKaser, A., Zeissig, S., & Blumberg, R. S. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101225 · Cited by 1,806 · see citing works
Epithelial NEMO links innate immunity to chronic intestinal inflammation
Nenci, A., Becker, C., Wullaert, A., Gareus, R., Loo, G., Danese, S., Huth, M., Nikolaev, A., Neufert, C. F., Madison, B., et al. (2007) · Nature · doi:10.1038/nature05698 · Cited by 1,077 · see citing works
Self-citationRIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL
Lawlor, K. E., Khan, N. R., Mildenhall, A., Gerlic, M., Croker, B. A., D’Cruz, A. A., Hall, C. M., Spall, S. K., Anderton, H., Masters, S. L., et al. (2015) · Nature Communications · doi:10.1038/ncomms7282 · Cited by 643 · see citing works
FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation
Welz, P.-S., Wullaert, A., Vlantis, K., Kondylis, V., Fernández-Majada, V., Ermolaeva, M., Kirsch, P., Sterner-Kock, A., van Loo, G., & Pasparakis, M. (2011) · Nature · doi:10.1038/nature10273 · Cited by 594 · cited 3× · see citing works
“As mice lacking FADD in IECs develop spontaneous colitis due to RIPK3-dependent epithelial cell necroptosis (Welz et al., 2011), we reasoned that necroptosis of IECs lacking both NEMO and FADD could trigger colitis in NEMOIEC-KO FADDIEC-KO mice.”
BackgroundInfluentialSelf-citationRIPK1 Regulates RIPK3-MLKL-Driven Systemic Inflammation and Emergency Hematopoiesis
Rickard, J. A., O’Donnell, J. A., Evans, J. M., Lalaoui, N., Poh, A. R., Rogers, T., Vince, J. E., Lawlor, K. E., Ninnis, R. L., Anderton, H., et al. (2014) · Cell · doi:10.1016/j.cell.2014.04.019 · Cited by 589 · see citing works
RIPK1 Blocks Early Postnatal Lethality Mediated by Caspase-8 and RIPK3
Dillon, C. P., Weinlich, R., Rodriguez, D. A., Cripps, J. G., Quarato, G., Gurung, P., Verbist, K. C., Brewer, T. L., Llambi, F., Gong, Y.-N., et al. (2014) · Cell · doi:10.1016/j.cell.2014.04.018 · Cited by 562 · see citing works
Self-citationRIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis
Dannappel, M., Vlantis, K., Kumari, S., Polykratis, A., Kim, C., Wachsmuth, L., Eftychi, C., Lin, J., Corona, T., Hermance, N., et al. (2014) · Nature · doi:10.1038/nature13608 · Cited by 534 · see citing works
Self-citationRegulation of tissue homeostasis by NF-κB signalling: implications for inflammatory diseases
Pasparakis, M. (2009) · Nature reviews. Immunology · doi:10.1038/nri2655 · Cited by 523 · see citing works
Self-citationEpithelial-cell-intrinsic IKK-β expression regulates intestinal immune homeostasis
Zaph, C., Troy, A. E., Taylor, B. C., Berman-Booty, L. D., Guild, K. J., Du, Y., Yost, E. A., Gruber, A. D., May, M. J., Greten, F. R., et al. (2007) · Nature · doi:10.1038/nature05590 · Cited by 496 · see citing works
Dondelinger, Y., Jouan-Lanhouet, S., Divert, T., Theatre, E., Bertin, J., Gough, P. J., Giansanti, P., Heck, A. J. R., Dejardin, E., Vandenabeele, P., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.07.032 · Cited by 431 · see citing works
Caspase-8 Blocks Kinase RIPK3-Mediated Activation of the NLRP3 Inflammasome
Kang, T.-B., Yang, S.-H., Toth, B., Kovalenko, A., & Wallach, D. (2013) · Immunity · doi:10.1016/j.immuni.2012.09.015 · Cited by 419 · see citing works
Polykratis, A., Hermance, N. M., Zelic, M., Roderick, J. E., KIM, C. S., Van, T.-M., Lee, T. H., Chan, F. K.-M., Pasparakis, M., & Kelliher, M. A. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400590 · Cited by 328 · see citing works
Self-citationRNA viruses promote activation of the NLRP3 inflammasome through a RIP1-RIP3-DRP1 signaling pathway
Wang, X., Jiang, W., Yan, Y., Gong, T., Han, J., Tian, Z., & Zhou, R. (2014) · Nature Immunology · doi:10.1038/ni.3015 · Cited by 323 · see citing works
RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis
Takahashi, N., Vereecke, L., Bertrand, M. J. M., Duprez, L., Berger, S. B., Divert, T., Gonçalves, A., Sze, M., Gilbert, B., Kourula, S., et al. (2014) · Nature · doi:10.1038/nature13706 · Cited by 318 · see citing works
Zeißig, S., Bojarski, C., Buergel, N., Mankertz, J., Zeitz, M., Fromm, M., & Schulzke, J. D. (2004) · Gut · doi:10.1136/gut.2003.036632 · Cited by 305 · see citing works
Microbiota, Disease, and Back to Health: A Metastable Journey
Blumberg, R. S., & Powrie, F. M. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004184 · Cited by 279 · see citing works
Alcamo, E., Mizgerd, J. P., Horwitz, B. H., Bronson, R. T., Beg, A. A., Scott, M. L., Doerschuk, C. M., Hynes, R. O., & Baltimore, D. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.3.1592 · Cited by 259 · see citing works
Hanson, E. P., Monaco-Shawver, L., Solt, L. A., Madge, L. A., Banerjee, P. P., May, M. J., & Orange, J. S. (2008) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2008.08.018 · Cited by 252 · see citing works
The Necroptosis Adaptor RIPK3 Promotes Injury-Induced Cytokine Expression and Tissue Repair
Moriwaki, K., Balaji, S., McQuade, T. J., Malhotra, N., Kang, J., & Chan, F. K.-M. (2014) · Immunity · doi:10.1016/j.immuni.2014.09.016 · Cited by 251 · see citing works
Paneth cells and innate mucosal immunity
Ouellette, A. J. (2010) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e32833dccde · Cited by 180 · see citing works
Steinbrecher, K. A., Harmel-Laws, E., Sitcheran, R., & Baldwin, A. S. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.4.2588 · Cited by 174 · see citing works
Opposing functions of IKKβ during acute and chronic intestinal inflammation
Eckmann, L., Nebelsiek, T., Fingerle, A. A., Dann, S. M., Mages, J., Lang, R., Robine, S., Kagnoff, M. F., Schmid, R. M., Karin, M., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808216105 · Cited by 166 · see citing works
Ireland, H., Houghton, C. A., Howard, L., & Winton, D. J. (2005) · Developmental Dynamics · doi:10.1002/dvdy.20446 · Cited by 139 · see citing works
Anti-TNF therapy in inflammatory bowel diseases: a huge review.
Peyrin‐Biroulet, L. (2010) · PubMed · Cited by 118 · see citing works
de Souza, H. S. P., Tortori, C., Castelo-Branco, M. T. L., Carvalho, A. T. P., Margallo, V. S., Delgado, C. F. S., Dines, I., & Elia, C. C. S. (2004) · International Journal of Colorectal Disease · doi:10.1007/s00384-004-0639-8 · Cited by 118 · see citing works
NEMO/IKKγ regulates an early NF-κB-independent cell-death checkpoint during TNF signaling
Legarda, D., Hase, H., O’Donnell, M. A., & Ting, A. T. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.41 · Cited by 111 · see citing works
Safe TNF-based antitumor therapy following p55TNFR reduction in intestinal epithelium
Hauwermeiren, F. V., Armaka, M., Karagianni, N., Kranidioti, K., Vandenbroucke, R. E., Loges, S., Roy, M. V., Staelens, J., Puimège, L., Palagani, A., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci65624 · Cited by 78 · see citing works
Diagnosis and Treatment in Anhidrotic Ectodermal Dysplasia with Immunodeficiency
Kawai, T., Nishikomori, R., & Heike, T. (2012) · Allergology International · doi:10.2332/allergolint.12-rai-0446 · Cited by 73 · see citing works
Fish, J. D., Duerst, R. E., Gelfand, E. W., Orange, J. S., & Bunin, N. (2008) · Bone Marrow Transplantation · doi:10.1038/bmt.2008.308 · Cited by 63 · see citing works
NEMO Inhibits Programmed Necrosis in an NFκB-Independent Manner by Restraining RIP1
O’Donnell, M. A., Hase, H., Legarda, D., & Ting, A. T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041238 · Cited by 62 · see citing works
Pai, S., Levy, O., Jabara, H. H., Glickman, J. N., Stoler‐Barak, L., Sachs, J., Nurko, S., Orange, J. S., & Geha, R. S. (2008) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2008.08.026 · Cited by 52 · see citing works
Permaul, P., Narla, A., Hornick, J. L., & Pai, S. (2009) · Immunologic Research · doi:10.1007/s12026-008-8085-2 · Cited by 51 · see citing works
Mizukami, T., Obara, M., Nishikomori, R., Kawai, T., Tahara, Y., Sameshima, N., Marutsuka, K., Nakase, H., Kimura, N., Heike, T., et al. (2011) · Journal of Clinical Immunology · doi:10.1007/s10875-011-9600-0 · Cited by 49 · see citing works
Epithelial apoptosis: Cause or consequence of ulcerative colitis?
Seidelin, J. B., & Nielsen, O. H. (2009) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365520903301212 · Cited by 36 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span
Misharin, A. V., Morales-Nebreda, L., Reyfman, P. A., Cuda, C. M., Walter, J. M., McQuattie-Pimentel, A. C., Chen, C.-I., Anekalla, K. R., Joshi, N., Williams, K. J. N., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20162152 · Cited by 1,133 · see citing works
Necroptosis in development, inflammation and disease
Weinlich, R., Oberst, A., Beere, H. M., & Green, D. R. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.149 · Cited by 1,016 · see citing works
Newton, K., Strasser, A., Kayagaki, N., & Dixit, V. M. (2024) · Cell · doi:10.1016/j.cell.2023.11.044 · Cited by 1,029 · see citing works
Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases
Yuan, J., Amin, P., & Ofengeim, D. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0093-1 · Cited by 967 · see citing works
A guide to cell death pathways
Yuan, J., & Ofengeim, D. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00689-6 · Cited by 972 · see citing works
Death by TNF: a road to inflammation
Loo, G., & Bertrand, M. J. M. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00792-3 · Cited by 977 · see citing works
The TNF Family of Ligands and Receptors: Communication Modules in the Immune System and Beyond
Dostert, C., Grusdat, M., Letellier, E., & Brenner, D. (2018) · Physiological Reviews · doi:10.1152/physrev.00045.2017 · Cited by 502 · see citing works
Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target
Mifflin, L., Ofengeim, D., & Yuan, J. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0071-y · Cited by 491 · see citing works
Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation
Jiao, H., Wachsmuth, L., Kumari, S., Schwarzer, R., Lin, J., Eren, R. O., Fisher, A. D., Lane, R. K., Young, G. R., Kassiotis, G., et al. (2020) · Nature · doi:10.1038/s41586-020-2129-8 · Cited by 493 · see citing works
Self-citationRole of the NFκB-signaling pathway in cancer
Xia, L., Tan, S., Zhou, Y., Lin, J., Wang, H., Oyang, L., Tian, Y., Liu, L., Su, M., Wang, H., et al. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s161109 · Cited by 461 · see citing works
Cell death in the gut epithelium and implications for chronic inflammation
Patankar, J. V., & Becker, C. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0326-4 · Cited by 421 · see citing works
Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity
Meier, P., Legrand, A. J., Adam, D., & Silke, J. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00674-x · Cited by 405 · see citing works
Necroptosis in development and diseasesPreprint
Shan, B., Pan, H., Najafov, A., & Yuan, J. (2018) · Genes & Development · doi:10.1101/gad.312561.118 · Cited by 345 · see citing works
Cell death pathways: intricate connections and disease implications
Kist, M., & Vucic, D. (2021) · The EMBO Journal · doi:10.15252/embj.2020106700 · Cited by 328 · see citing works
MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death
Jaco, I., Annibaldi, A., Lalaoui, N., Wilson, R., Tenev, T., Laurien, L., KIM, C. S., Jamal, K., John, S. W., Liccardi, G., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.05.003 · Cited by 320 · see citing works
Self-citationWebster, J. D., & Vucic, D. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00365 · Cited by 315 · see citing works
Checkpoints in TNF-Induced Cell Death: Implications in Inflammation and Cancer
Annibaldi, A., & Meier, P. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.11.002 · Cited by 287 · see citing works
Cell death and inflammation during obesity: “Know my methods, WAT(son)”
Hildebrandt, X., Ibrahim, M. A., & Peltzer, N. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-01062-4 · Cited by 283 · see citing works
Schwarzer, R., Jiao, H., Wachsmuth, L., Tresch, A., & Pasparakis, M. (2020) · Immunity · doi:10.1016/j.immuni.2020.04.002 · Cited by 277 · see citing works
Self-citationMore to Life than NF-κB in TNFR1 Signaling
Ting, A. T., & Bertrand, M. J. M. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.06.002 · Cited by 254 · see citing works
Intracellular regulation of TNF activity in health and disease
Varfolomeev, E. E., & Vucic, D. (2016) · Cytokine · doi:10.1016/j.cyto.2016.08.035 · Cited by 247 · see citing works
Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation
Laurien, L., Nagata, M., Schünke, H., Delanghe, T., Wiederstein, J. L., Kumari, S., Schwarzer, R., Corona, T., Krüger, M., Bertrand, M. J. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15466-8 · Cited by 240 · see citing works
Self-citationKondylis, V., Kumari, S., Vlantis, K., & Pasparakis, M. (2017) · Immunological Reviews · doi:10.1111/imr.12550 · Cited by 226 · see citing works
Self-citationMK2 phosphorylation of RIPK1 regulates TNF-mediated cell death
Dondelinger, Y., Delanghe, T., Rojas-Rivera, D., Priem, D., Delvaeye, T., Bruggeman, I., Herreweghe, F. V., Vandenabeele, P., & Bertrand, M. J. M. (2017) · Nature Cell Biology · doi:10.1038/ncb3608 · Cited by 202 · see citing works
Dondelinger, Y., Delanghe, T., Priem, D., Wynosky-Dolfi, M. A., Sorobetea, D., Rojas‐Rivera, D., Giansanti, P., Roelandt, R., Gropengießer, J., Ruckdeschel, K., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09690-0 · Cited by 200 · see citing works
The NF-κB signaling system in the immunopathogenesis of inflammatory bowel disease
Mukherjee, T., Kumar, N., Chawla, M., Philpott, D. J., & Basak, S. (2024) · Science Signaling · doi:10.1126/scisignal.adh1641 · Cited by 204 · see citing works
Gut epithelial TSC1/mTOR controls RIPK3-dependent necroptosis in intestinal inflammation and cancer
Xie, Y., Zhao, Y., Shi, L., Li, W., Chen, K., Li, M., Chen, X., Zhang, H., Li, T., Matsuzawa, Y., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133264 · Cited by 198 · see citing works
Inflammatory Bowel Disease: A Review of Pre-Clinical Murine Models of Human Disease
Katsandegwaza, B., Horsnell, W. G. C., & Smith, K. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169344 · Cited by 191 · see citing works
Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis
Wegner, K. W., Saleh, D., & Degterev, A. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.12.005 · Cited by 188 · see citing works
Schwarzer, R., Laurien, L., & Pasparakis, M. (2020) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2020.02.004 · Cited by 161 · see citing works
Self-citationRIP1 inhibition blocks inflammatory diseases but not tumor growth or metastases
Patel, S. D., Webster, J. D., Varfolomeev, E. E., Kwon, Y. C., Cheng, J. H., Zhang, J., Dugger, D. L., Wickliffe, K. E., Maltzman, A., Sujatha-Bhaskar, S., et al. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0347-0 · Cited by 151 · see citing works
RIPK1 Kinase-Dependent Death: A Symphony of Phosphorylation Events
Delanghe, T., Dondelinger, Y., & Bertrand, M. J. M. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.12.009 · Cited by 148 · see citing works
Amin, P. P., Florez, M. A., Najafov, A., Pan, H., Geng, J., Ofengeim, D., Dziedzic, S. A., Wang, H., Barrett, V. J., Ito, Y., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1806973115 · Cited by 143 · see citing works
A20 and cell death-driven inflammation
Priem, D., van Loo, G., & Bertrand, M. J. M. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.03.001 · Cited by 139 · see citing works
Cell death checkpoints in the TNF pathway
Huyghe, J., Priem, D., & Bertrand, M. J. M. (2023) · Trends in Immunology · doi:10.1016/j.it.2023.05.007 · Cited by 143 · see citing works
Novel insights into microbiome in colitis and colorectal cancer
Yang, Y., & Jobin, C. (2017) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000399 · Cited by 129 · see citing works
Diverse ubiquitin linkages regulate RIP kinases-mediated inflammatory and cell death signaling
Witt, A., & Vucic, D. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.33 · Cited by 126 · see citing works
The regulation of necroptosis by post-translational modifications
Meng, Y., Sandow, J. J., Czabotar, P. E., & Murphy, J. M. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-020-00722-7 · Cited by 127 · see citing works
Control of Cell Death in Health and Disease
Kayagaki, N., Webster, J. D., & Newton, K. (2023) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-051022-014433 · Cited by 124 · see citing works
A RIPK3-PGE2 Circuit Mediates Myeloid-Derived Suppressor Cell–Potentiated Colorectal Carcinogenesis
Yan, G., Zhao, H., Zhang, Q., Zhou, Y. J., Wu, L., Lei, J., Wang, X., Zhang, J., Zhang, X., Zheng, L., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-3962 · Cited by 120 · see citing works
Eftychi, C., Schwarzer, R., Vlantis, K., Wachsmuth, L., Basic, M., Wagle, P., Neurath, M. F., Becker, C., Bleich, A., & Pasparakis, M. (2019) · Immunity · doi:10.1016/j.immuni.2019.06.008 · Cited by 118 · see citing works
Self-citationPaneth cells as the cornerstones of intestinal and organismal health: a primer
Wallaeys, C., García-González, N., & Libert, C. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202216427 · Cited by 121 · see citing works
RIPK1 can mediate apoptosis in addition to necroptosis during embryonic development
Zhang, X., Dowling, J. P., & Zhang, J. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1490-8 · Cited by 112 · see citing works
The in vivo evidence for regulated necrosis
Tonnus, W., & Linkermann, A. (2017) · Immunological Reviews · doi:10.1111/imr.12551 · Cited by 109 · see citing works
Multitasking Kinase RIPK1 Regulates Cell Death and InflammationPreprint
Newton, K. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a036368 · Cited by 106 · see citing works
Current translational potential and underlying molecular mechanisms of necroptosis
Molnár, T., Mázló, A., Tslaf, V., Szöllősi, A. G., Emri, G., & Koncz, G. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-2094-z · Cited by 107 · see citing works
Dziedzic, S. A., Su, Z., Barrett, V. J., Najafov, A., Mookhtiar, A. K., Amin, P. P., Pan, H., Sun, L., Zhu, H., Ma, A. I., et al. (2017) · Nature Cell Biology · doi:10.1038/s41556-017-0003-1 · Cited by 98 · see citing works
Li, X., Zhang, M., Huang, X., Liang, W. P., Li, G., Lu, X., Li, Y., Pan, H., Shi, L., Zhu, H., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19935-y · Cited by 99 · see citing works
Tang, Y., Tu, H., Zhang, J., Zhao, X., Wang, Y., Qin, J., & Lin, X. (2019) · Nature Communications · doi:10.1038/s41467-019-12033-8 · Cited by 96 · see citing works
Zhang, X., Zhang, H., Xu, C., Li, M., Li, M., Pu, W., Pu, W., Zhou, B., Wang, H., Li, D., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11839-w · Cited by 94 · see citing works
Mannion, J., Gifford, V., Bellenie, B. R., Fernando, W., Garcia, L. R., Wilson, R., John, S. W., Udainiya, S., Patin, E. C., Tiu, C., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.04.025 · Cited by 92 · see citing works
Roles of RIPK1 as a stress sentinel coordinating cell survival and immunogenic cell death
Clucas, J., & Meier, P. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00623-w · Cited by 92 · see citing works
Martin‐Gallausiaux, C., Garcia-Weber, D., Lashermes, A., Larraufie, P., Marinelli, L., Teixeira, V., Rolland, A., Béguet-Crespel, F., Brochard, V., Quatremare, T., et al. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2110639 · Cited by 84 · see citing works
Gut Microbiome Alterations During HIV/SIV Infection: Implications for HIV Cure
Crakes, K. R., & Jiang, G. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.01104 · Cited by 83 · see citing works
PANoptosis: A New Insight Into Oral Infectious Diseases
Jiang, W., Deng, Z., Dai, X., & Zhao, W. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.789610 · Cited by 84 · see citing works
NEMO Links Nuclear Factor-κB to Human Diseases
Maubach, G., Schmädicke, A.-C., & Naumann, M. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.10.004 · Cited by 77 · see citing works
Moving towards a systems-based classification of innate immune-mediated diseases
Savic, S., Caseley, E. A., & McDermott, M. (2020) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-0377-5 · Cited by 79 · see citing works
Shamoon, M., Martin, N. M., & O'Brien, C. L. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104344 · Cited by 73 · see citing works
Genetic Regulation of RIPK1 and Necroptosis
Xu, D., Zou, C., & Yuan, J. (2021) · Annual Review of Genetics · doi:10.1146/annurev-genet-071719-022748 · Cited by 76 · see citing works
Geng, R., Tan, X., Wu, J., Pan, Z., Yi, M., Shi, W., Liu, R., Yao, C., Wang, G., Lin, J., et al. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.400 · Cited by 73 · see citing works
Chen, S., Liu, H., Li, Z., Tang, J., Huang, B. Q., Zhi, F., & Zhao, X. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03843-0 · Cited by 68 · see citing works
Primidone blocks RIPK1-driven cell death and inflammation
Riebeling, T., Jamal, K., Wilson, R., Kolbrink, B., von Samson‐Himmelstjerna, F. A., Moerke, C., Garcia, L. R., Dahlke, E., Michels, F., Lühder, F., et al. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00690-y · Cited by 64 · see citing works
A20 and ABIN-1 synergistically preserve intestinal epithelial cell survival
Kattah, M. G., Shao, L., Rosli, Y. Y., Shimizu, H., Whang, M. I., Advincula, R., Achacoso, P., Shah, S. B., Duong, B. H., Onizawa, M., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20180198 · Cited by 59 · see citing works
Death Receptors and Their Ligands in Inflammatory Disease and CancerPreprint
Annibaldi, A., & Walczak, H. (2020) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a036384 · Cited by 59 · see citing works
Self-citationZhao, Q., Yu, X., Zhang, H., Liu, Y., Zhang, X., Wu, X., Xie, Q., Li, M., Ying, H., & Zhang, H. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.011 · Cited by 49 · see citing works
The roles of ubiquitination in extrinsic cell death pathways and its implications for therapeutics
Seo, J., Kim, M. W., Bae, K., Lee, S. C., Song, J., & Lee, E. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.11.012 · Cited by 47 · see citing works
Li, Z., Yan, Z., Lan, F., Dong, Y.-Q., & Xiong, Y. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.05.085 · Cited by 47 · see citing works
Inflammatory cell death in intestinal pathologies
Sharma, D., & Kanneganti, T. (2017) · Immunological Reviews · doi:10.1111/imr.12602 · Cited by 48 · see citing works
Luo, X., Zhang, X., Gan, L., Zhou, C., Zhao, T., Zeng, T., Liu, S., Xiao, Y., Yu, J. C., & Zhao, F. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13879 · Cited by 46 · see citing works
The many faces of tumor necrosis factor signaling in the intestinal epithelium
Delgado, M. E., & Brunner, T. (2019) · Genes and Immunity · doi:10.1038/s41435-019-0057-0 · Cited by 45 · see citing works
Gao, J., Liu, M., Guo, H., Zhu, K.-C., Liu, B., Liu, B.-S., Zhang, N., & Zhang, D. (2022) · Antioxidants · doi:10.3390/antiox11091809 · Cited by 45 · see citing works
Innate and adaptive immune abnormalities underlying autoimmune diseases: the genetic connections
Chi, X., Huang, M., Tu, H., Zhang, B., Lin, X., Xu, H., Dong, C., & Hu, X. (2023) · Science China Life Sciences · doi:10.1007/s11427-021-2187-3 · Cited by 45 · see citing works
25 years of research put RIPK1 in the clinic
Liu, L., & Lalaoui, N. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.08.007 · Cited by 45 · see citing works
Heppert, J. K., Davison, J. M., Kelly, C., Mercado, G. P., Lickwar, C. R., & Rawls, J. F. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00357-6 · Cited by 43 · see citing works
FLAME: A Web Tool for Functional and Literature Enrichment Analysis of Multiple Gene Lists
Thanati, F., Karatzas, E., Baltoumas, F. A., Stravopodis, D. J., Eliopoulos, A. G., & Pavlopoulos, G. A. (2021) · Biology · doi:10.3390/biology10070665 · Cited by 45 · see citing works
Xu, Y., Lin, F., Liao, G., Sun, J., Chen, W., & Zhang, L. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-03981-4 · Cited by 43 · see citing works
Gastrointestinal Disorders Associated with Primary Immunodeficiency Diseases
Hartono, S. P., Ippoliti, M. R., Mastroianni, M. A., Torres, R., & Rider, N. L. (2018) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-018-8689-9 · Cited by 41 · see citing works
RIP1 kinase activity is critical for skin inflammation but not for viral propagation
Webster, J. D., Kwon, Y. C., Park, S., Zhang, H., Corr, N., Ljumanovic, N., Adedeji, A. O., Varfolomeev, E. E., Goncharov, T., Preston, J., et al. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ma1219-398r · Cited by 37 · see citing works
Genetic inactivation of RIP1 kinase does not ameliorate disease in a mouse model of ALS
Domínguez, S. L., Varfolomeev, E. E., Brendza, R. P., Stark, K., Tea, J. S., Imperio, J., Ngu, H., Earr, T., Foreman, O., Webster, J. D., et al. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00625-7 · Cited by 37 · see citing works
Microbial signals, MyD88, and lymphotoxin drive TNF-independent intestinal epithelial tissue damage
Rusu, I., Mennillo, E., Li, Z., Bain, J. L., Sun, X., Ly, K., Rosli, Y. Y., Naser, M., Wang, Z., Advincula, R., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci154993 · Cited by 36 · see citing works
An immunohistochemical atlas of necroptotic pathway expression
Chiou, S., Al‐Ani, A., Pan, Y., Patel, K. M., Kong, I. Y., Whitehead, L. W., Light, A., Young, S. N., Barrios, M. H., Sargeant, C. J., et al. (2024) · EMBO Molecular Medicine · doi:10.1038/s44321-024-00074-6 · Cited by 36 · see citing works
Small-Molecule Drugs for the Treatment of Inflammatory Bowel Disease
Fitzpatrick, L. R., & Woldemariam, T. Z. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.12404-7 · Cited by 35 · see citing works
Decreased linear ubiquitination of NEMO and FADD on apoptosis with caspase-mediated cleavage of HOIP
Gotō, E., & Tokunaga, F. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.02.040 · Cited by 34 · see citing works
Li, C., Chen, Y., Zhu, H.-T., Zhang, X., Han, L., Zhao, Z., Wang, J., Ning, L., Zhou, W., Lü, C., et al. (2020) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjaa016 · Cited by 35 · see citing works
RIP1 post-translational modifications
Varfolomeev, E., & Vucic, D. (2022) · Biochemical Journal · doi:10.1042/bcj20210725 · Cited by 35 · see citing works
Ferulic acid relieved ulcerative colitis by inhibiting the TXNIP/NLRP3 pathway in rats
Sheng, Y., Qian, H., Zhang, D., & Jiang, Z. (2022) · Cell Biology International · doi:10.1002/cbin.11935 · Cited by 34 · see citing works
Hausmann, A., Russo, G., Grossmann, J., Zünd, M., Schwank, G., Aebersold, R. H., Liu, Y., Sellin, M. E., & Hardt, W. (2020) · Cellular Microbiology · doi:10.1111/cmi.13191 · Cited by 32 · see citing works
Chen, X., Cheng, B., Dai, D., Wu, Y., Feng, Z., Tong, C., Wang, X., & Zhao, J. (2021) · Cell Death Discovery · doi:10.1038/s41420-021-00411-5 · Cited by 33 · see citing works
Intercrypt sentinel macrophages tune antibacterial NF-κB responses in gut epithelial cells via TNF
Hausmann, A., Felmy, B., Kunz, L., Kroon, S., Berthold, D. L., Ganz, G., Sandu, I., Nakamura, T., Zangger, N. S., Zhang, Y., et al. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20210862 · Cited by 33 · see citing works
Self-citationZhou, P., Li, M., Han, X., Bi, Y., Zhang, W., Wu, Z., & Wu, G. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.29238 · Cited by 32 · see citing works
Phytotherapies in inflammatory bowel disease
Ganji‐Arjenaki, M., & Rafieian‐Kopaei, M. (2019) · Journal of Research in Medical Sciences · doi:10.4103/jrms.jrms_590_17 · Cited by 32 · see citing works
Stolzer, I., Kaden-Volynets, V., Ruder, B., Letizia, M., Bittel, M., Rausch, P., Basic, M., Bleich, A., Baines, J. F., Neurath, M. F., et al. (2019) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izz142 · Cited by 31 · see citing works
NF-κB inhibition in keratinocytes causes RIPK1-mediated necroptosis and skin inflammation
Kumari, S., Van, T.-M., Preukschat, D., Schünke, H., Basic, M., Bleich, A., Klein, U., & Pasparakis, M. (2021) · Life Science Alliance · doi:10.26508/lsa.202000956 · Cited by 31 · see citing works
Self-citationAntioxidant and food additive BHA prevents TNF cytotoxicity by acting as a direct RIPK1 inhibitor
Delanghe, T., Huyghe, J., Lee, S., Priem, D., Coillie, S. V., Gilbert, B., Choi, S. M., Vandenabeele, P., Degterev, A., Cuny, G. D., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03994-0 · Cited by 31 · see citing works
Ghazavi, F., Huysentruyt, J., Coninck, J. D., Kourula, S., Martens, S., Hassannia, B., Wartewig, T., Divert, T., Roelandt, R., Popper, B., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2024508119 · Cited by 31 · see citing works
Targeting RIP Kinases in Chronic Inflammatory Disease
Speir, M., Djajawi, T. M., Conos, S. A., Tye, H., & Lawlor, K. E. (2021) · Biomolecules · doi:10.3390/biom11050646 · Cited by 29 · see citing works
Chen, Y., Zhang, Y., Dai, Y.-C., & Tang, Z. (2018) · World Journal of Gastroenterology · doi:10.3748/wjg.v24.i13.1398 · Cited by 29 · see citing works
Immune cell-derived signals governing epithelial phenotypes in homeostasis and inflammation
Hausmann, A., Steenholdt, C., Nielsen, O. H., & Jensen, K. B. (2024) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2024.01.001 · Cited by 30 · see citing works
Du, J., & Wang, Z. (2024) · Biomedicines · doi:10.3390/biomedicines12071525 · Cited by 28 · see citing works
- Authors
- Vlantis, K., Wullaert, A., Polykratis, A., Kondylis, V., Dannappel, M., Schwarzer, R., Welz, P., Corona, T., Walczak, H., Weih, F., Klein, U., Kelliher, M., & Pasparakis, M.
- Affiliations
- University of Cologne (DE)
- University College London (GB)
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Herbert Irving Comprehensive Cancer Center (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Pasparakis, Manolis
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 44
- Issue
- 3
- Pages
- 553-567
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4803910
- OpenAlex
- W2299243013
- Cited by
- 189
- References
- 38
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 22 · 2023: 19 · 2022: 16 · 2021: 20 · 2020: 24 · 2019: 20 · 2018: 25 · 2017: 19 · 2016: 4
- FWCI
- 9.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Immunity (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by-nc-nd)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- Funders
- European Commission (223151, 223404)
- Deutsche Forschungsgemeinschaft (SPP-1656, SFB 670)
- Universität Ulm
- National Institutes of Health
- Genentech
- National Institute of Allergy and Infectious Diseases (R01AI075118)
- FP7 Ideas: European Research Council (323040)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- NEMO, RIPK1, NF-κB, intestinal epithelial cells, epithelial cell death, chronic intestinal inflammation, colitis, inflammatory bowel disease, FADD, RIPK3, microbiota, RelA, c-Rel, RelB, RIPK1 inhibitors
- MeSH terms
- Animals, Cells, Cultured, Humans, Intestinal Mucosa, Mice, Inbred C57BL, Inflammatory Bowel Diseases, NF-kappa B, Apoptosis, Mice, Knockout, Paneth Cells, Proto-Oncogene Proteins c-rel, Intracellular Signaling Peptides and Proteins, Mice, Transcription Factor RelB, Transcription Factor RelA, Fas-Associated Death Domain Protein, Receptor-Interacting Protein Serine-Threonine Kinases
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