The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis
Open accessAbstract
Necroptosis has emerged as an important pathway of programmed cell death in embryonic development, tissue homeostasis, immunity and inflammation. RIPK1 is implicated in inflammatory and cell death signalling and its kinase activity is believed to drive RIPK3-mediated necroptosis. Here we show that kinase-independent scaffolding RIPK1 functions regulate homeostasis and prevent inflammation in barrier tissues by inhibiting epithelial cell apoptosis and necroptosis. Intestinal epithelial cell (IEC)-specific RIPK1 knockout caused IEC apoptosis, villus atrophy, loss of goblet and Paneth cells and premature death in mice. This pathology developed independently of the microbiota and of MyD88 signalling but was partly rescued by TNFR1 (also known as TNFRSF1A) deficiency. Epithelial FADD ablation inhibited IEC apoptosis and prevented the premature death of mice with IEC-specific RIPK1 knockout. However, mice lacking both RIPK1 and FADD in IECs displayed RIPK3-dependent IEC necroptosis, Paneth cell loss and focal erosive inflammatory lesions in the colon. Moreover, a RIPK1 kinase inactive knock-in delayed but did not prevent inflammation caused by FADD deficiency in IECs or keratinocytes, showing that RIPK3-dependent necroptosis of FADD-deficient epithelial cells only partly requires RIPK1 kinase activity. Epidermis-specific RIPK1 knockout triggered keratinocyte apoptosis and necroptosis and caused severe skin inflammation that was prevented by RIPK3 but not FADD deficiency. These findings revealed that RIPK1 inhibits RIPK3-mediated necroptosis in keratinocytes in vivo and identified necroptosis as a more potent trigger of inflammation compared with apoptosis. Therefore, RIPK1 is a master regulator of epithelial cell survival, homeostasis and inflammation in the intestine and the skin.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Likewise, the absence of Ripk1 from keratinocytes promotes spontaneous necroptosis and consequent cutaneous inflammation, which can be prevented by the co-deletion of Ripk3, Mlkl, or Zbp1 but not Fadd [440, 502].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [502]
In the citing paper
“Conditional knockout mouse models demonstrate the key role of RIPK1 for the preservation of intestinal and cutaneous homeostasis and survival [502, 503].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [502]
In the citing paper
“In particular, mice lacking Ripk1 in intestinal epithelial cells display increased rates of spontaneous CASP8-driven apoptosis and develop severe inflammatory lesions leading to premature death, a detrimental phenotype that can be prevented by co-deleting Fadd or (to a lesser degree) Tnfrsf1a [502].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [502]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204
IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K. J., Takeuchi, O., & Akira, S. (2005) · Nature Immunology · doi:10.1038/ni1243 · Cited by 2,562
IKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer
Greten, F. R., Eckmann, L., Greten, T. F., Park, J. M., Li, Z.-W., Egan, L. J., Kagnoff, M. F., & Karin, M. (2004) · Cell · doi:10.1016/j.cell.2004.07.013 · Cited by 2,433
Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function.
Adachi, O., Kawai, T., Takeda, K., Matsumoto, M., Tsutsui, H., Sakagami, M., Nakanishi, K., & Akira, S. (1998) · Immunity · doi:10.1016/s1074-7613(00)80596-8 · Cited by 2,358
Improving CRISPR-Cas nuclease specificity using truncated guide RNAs
Fu, Y., Sander, J. D., Reyon, D., Cascio, V. M., & Joung, J. K. (2014) · Nature Biotechnology · doi:10.1038/nbt.2808 · Cited by 1,993
Kaser, A., Zeissig, S., & Blumberg, R. S. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101225 · Cited by 1,806
Regulated necrosis: the expanding network of non-apoptotic cell death pathways
Berghe, T. V., Linkermann, A., Jouan-Lanhouet, S., Walczak, H., & Vandenabeele, P. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3737 · Cited by 1,735
Pfeffer, K., Matsuyama, T., Kündig, T. M., Wakeham, A., Kishihara, K., Shahinian, A., Wiegmann, K., Ohashi, P. S., Krönke, M., & Mak, T. W. (1993) · Cell · doi:10.1016/0092-8674(93)90134-c · Cited by 1,677
Schwenk, F., Baron, U., & Rajewsky, K. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.24.5080 · Cited by 1,289
Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis
Oberst, A., Dillon, C. P., Weinlich, R., McCormick, L. L., Fitzgerald, P., Pop, C., Hakem, R., Salvesen, G. S., & Green, D. R. (2011) · Nature · doi:10.1038/nature09852 · Cited by 1,278
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–400 of 541
Necroptosis in the periodontal homeostasis: Signals emanating from dying cells
Li, J., Ke, X., Yan, F., Lei, L., & Li, H. (2017) · Oral Diseases · doi:10.1111/odi.12722 · Cited by 24
Mikuda, N., Schmidt‐Ullrich, R., Kärgel, E., Golusda, L., Wolf, J., Höpken, U. E., Scheidereit, C., Kühl, A. A., & Kolesnichenko, M. (2020) · The Journal of Pathology · doi:10.1002/path.5437 · Cited by 25
“Dysfunction of Paneth cells or loss through necroptosis or apoptosis contributes to the pathogenesis of IBD [43,44].”
BackgroundZhang, T., Shi, L., Li, Y., Mu, W., Zhang, H., Li, Y., Wang, X., Zhao, W., Qi, Y., & Liu, L. (2020) · Journal of Radiation Research · doi:10.1093/jrr/rraa093 · Cited by 24
“Radiation-induced gastrointestinal injury is histopathologically characterized by crypt cell destruction, decreased villous height and number, and impaired epithelial barrier function [8].”
BackgroundMin, W., Sun, L., Li, B., Gao, X., Zhang, S., & Zhao, Y. (2021) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.3727/096504021x16203818567367 · Cited by 26
Design, synthesis, and evaluation of potent RIPK1 inhibitors with in vivo anti-inflammatory activity
Li, Z., Hao, Y., Yang, C., Yang, Q., Wu, S., Ma, H., Tian, S., Lu, H., Wang, J., Yang, T., et al. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.114036 · Cited by 24
The cell death response to enteropathogenicEscherichia coliinfection
Lung, T. W. F., Pearson, J. S., Schuelein, R., & Hartland, E. L. (2014) · Cellular Microbiology · doi:10.1111/cmi.12371 · Cited by 24
“Most recently, RIPK1 was shown to play a dual regulatory role in gut homoeostasis by inhibiting both apoptosis and necroptosis in intestinal epithelial cells through its scaffolding function (Dannappel et al., 2014; Takahashi et al., 2014).”
BackgroundZhang, C., Luo, Y., He, Q., Liu, S., He, A., & Yan, J. (2019) · Clinical Science · doi:10.1042/cs20181081 · Cited by 26
RIPK1 suppresses apoptosis mediated by TNF and caspase-3 in intervertebral discs
Qiu, X., Zhuang, M., Lu, Z., Liu, Z., Cheng, D., Zhu, C., & Liu, J. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-1886-3 · Cited by 24
A shorter splicing isoform antagonizes ZBP1 to modulate cell death and inflammatory responses
Nagata, M., Schäfer, Y. C., Wachsmuth, L., & Pasparakis, M. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00238-7 · Cited by 22
“Ripk1 fl / fl (Dannappel et al, 2014) and K14-cre (Hafner et al, 2004) mice were described previously.”
BackgroundSelf-citationRIPK1: A rising star in inflammatory and neoplastic skin diseases
Jin, L., Liu, P., Yin, M., Zhang, M., Kuang, Y., & Zhu, W. (2020) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2020.06.001 · Cited by 23
Necroptotic movers and shakers: cell types, inflammatory drivers and diseases
Weir, A. L., Hughes, S. A., Rashidi, M., Hildebrand, J. M., & Vince, J. E. (2020) · Current Opinion in Immunology · doi:10.1016/j.coi.2020.09.008 · Cited by 22
Impact of myeloid RIPK1 gene deletion on atherogenesis in ApoE-deficient mice
Coornaert, I., Puylaert, P., Marcassoli, G., Grootaert, M. O. J., Vandenabeele, P., Meyer, G. R. Y. D., & Martinet, W. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.02.021 · Cited by 23
RIPK1-Associated Inborn Errors of Innate Immunity
Zhang, J., Jin, T., Aksentijevich, I. A., & Zhou, Q. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.676946 · Cited by 22
“Similarly, Ripk1 deletion in epidermis cell induces keratinocyte apoptosis and necroptosis, resulting in severe skin inflammation (42).”
BackgroundTherapy Targets SARS-CoV-2 Infection-Induced Cell Death
Zhu, Z., Shi, J., Li, L., Wang, J., Zhao, Y., & Ma, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.870216 · Cited by 23
Dagenais, M., Dupaul-Chicoine, J., Champagne, C., Skeldon, A. M., Morizot, A., & Saleh, M. (2015) · Mucosal Immunology · doi:10.1038/mi.2015.46 · Cited by 24
“IECspecific targeted deletion of effectors of the NF-kB pathway, such as NEMO (NF-kB essential modulator) or both IKKa/ IKKb, results in spontaneous colitis caused by excessive 154 VOLUME 9 NUMBER 1 | JANUARY 2016 |www.nature.com/mi apoptosis.70 Similarly, exacerbated IEC apoptosis leads to spontaneous intestinal infl…”
BackgroundInfluentialClinical phenotype of a Chinese patient with RIPK1 deficiency due to novel mutation
Lin, L., Wang, Y., Liu, L., Ying, W., Wang, W., Sun, B., Sun, J., & Wang, X. (2019) · Genes & Diseases · doi:10.1016/j.gendis.2019.10.008 · Cited by 21
Ma, S., Xu, L., Chen, L., Sun, X., Hu, F., Gong, Y., Yang, R., Li, J., Wang, Q., Huang, S., et al. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115165 · Cited by 23
Wen, H., Zhang, X., Li, Q., Huang, J., Liu, G., Zhao, J., Liu, Y., Shen, L., Li, Y., Yang, K., et al. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/4877275 · Cited by 21
“A series of physiological factors may contribute to induce intestinal hyperpermeability, and abnormal apoptosis of intestinal epithelial cells can lead to damage of the intestinal barrier as well as directly increase permeability [9].”
BackgroundZhou, Q., Zheng, Z., Wang, X., Li, W., Wang, L., Yin, C., Zhang, Q., & Wang, Q. (2023) · Neurochemical Research · doi:10.1007/s11064-023-03871-6 · Cited by 20
“Nevertheless, recent studies had also shown that necroptosis might precede and trigger the inflammatory response[32], and that RIPK3 deficiency prevented epithelial cell necroptosis and inflammation in both the intestinal and skin of these mice[33].”
BackgroundRIPK1 and PGAM5 Control Leishmania Replication through Distinct Mechanisms
Luz, N. F., Balaji, S., Okuda, K., Barreto, A. S., Bertin, J., Gough, P. J., Gazzinelli, R. T., de Almeida, R. P., Bozza, M. T., Borges, V. M., et al. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502492 · Cited by 21
TNF Signaling through RIP1 Kinase Enhances SN38-Induced Death in Colon Adenocarcinoma
Cabal‐Hierro, L., & O'Dwyer, P. J. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0329 · Cited by 21
“In the context of colon epithelium, RIP1 has been proposed as a master regulator of homeostasis and cell survival (38, 39).”
BackgroundVery early onset IBD: novel genetic aetiologies
Batura, V., & Muise, A. M. (2018) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0000000000000486 · Cited by 22
Intestinal immunoregulation: lessons from human mendelian diseases
Charbit‐Henrion, F., Parlato, M., Malamut, G., Ruemmele, F. M., & Cerf–Bensussan, N. (2021) · Mucosal Immunology · doi:10.1038/s41385-021-00398-3 · Cited by 23
“Ripk1 mice as well as mice selectively depleted in Ripk1 in IEC showed severe intestinal lesions and extensive IEC death that were ascribed to loss of the scaffolding function of RIPK1 and reduced stability of the survival proteins TRAF2 and c-IAP1.(77) In contrast, there is no evidence of extensive epithelial cell de…”
BackgroundThe importance of murine phospho-MLKL-S345 in situ detection for necroptosis assessment in vivo
Kelepouras, K., Saggau, J., Varanda, A. B., Zrilić, M., Kiefer, C., Rakhsh-Khorshid, H., Lisewski, I., Uranga-Murillo, I., Arias, M. A., Pardo, J., et al. (2024) · Cell Death and Differentiation · doi:10.1038/s41418-024-01313-6 · Cited by 23
“…pyroptosis [35], it has paradoxically been utilised even in models in which the deletion of FADD or Casp8 and RIPK1 leads to necroptosis-induced lethality which has been genetically demonstrated to occur in a caspase-independent manner as completely rescued by RIPK3 co-deletion [58 – 60].”
RIPK3 in necroptosis and cancer
Morgan, M. J., & Kim, Y. (2025) · Molecules and Cells · doi:10.1016/j.mocell.2025.100199 · Cited by 21
Androulidaki, A., Wachsmuth, L., Polykratis, A., & Pasparakis, M. (2018) · PLoS ONE · doi:10.1371/journal.pone.0194048 · Cited by 22
Self-citationLian, N., Chen, Y., Chen, S., Xiao, T., Song, C., Ke, Y., Wei, X., Gong, C., Yu, H., Gu, H., et al. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01228-6 · Cited by 20
“[35] found that apoptosis and necroptosis were triggered in keratinocytes of RIPK1 mice.”
BackgroundTumor necrosis factor is a necroptosis-associated alarmin
Pinci, F., Gaidt, M. M., Jung, C., Nagl, D., Kuut, G., & Hornung, V. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1074440 · Cited by 20
Fn14 and TNFR2 as regulators of cytotoxic TNFR1 signaling
Siegmund, D., Zaitseva, O., & Wajant, H. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1267837 · Cited by 20
Acosta, M. P., Jeong, S., Utrero‐Rico, A., Goncharov, T., Webster, J. D., Holler, E., Morales, G., Dellepiane, S., Levine, J. E., Rothenberg, M. E., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adf8366 · Cited by 20
Significance of Necroptosis in Cartilage Degeneration
Khaleque, M. A., Kim, J.-H., Tanvir, M. A. H., Park, J., & Kim, Y. (2024) · Biomolecules · doi:10.3390/biom14091192 · Cited by 20
“Necroptosis has been identified as a crucial factor in cartilage degeneration, and specific protein molecules mediate this process [108,109].”
BackgroundTAK1 regulates Paneth cell integrity partly through blocking necroptosis
Simmons, A., Kajino‐Sakamoto, R., & Ninomiya‐Tsuji, J. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.98 · Cited by 20
“Recently, intestinal epithelial-specific deletion of Ripk1 was reported to deplete Paneth cells.(36,37) Thus, deletion of either Tak1 or Ripk1 results in Paneth cell loss.”
BackgroundEmerging Roles for RIPK1 and RIPK3 in Pathogen-Induced Cell Death and Host Immunity
Saleh, D., & Degterev, A. (2015) · Current topics in microbiology and immunology · doi:10.1007/82_2015_449 · Cited by 19
“Analogous to observations made in intestinal epithelia, anti-apoptotic ubiquitin ligase, cIAP1, is rapidly diminished following TNF-α exposure to RIPK1 to primary keratinocytes (Dannappel et al. 2014).”
BackgroundResultInfluentialDietschmann, A., Schruefer, S., Westermann, S., Henkel, F. D. R., Castiglione, K., Willebrand, R., Adam, J., Ruland, J., Lang, R., Sheppard, D. C., et al. (2022) · mBio · doi:10.1128/mbio.01239-22 · Cited by 19
Ratovitski, E. A. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.04.020 · Cited by 21
Salvadores, N., & Court, F. A. (2020) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2020.1758668 · Cited by 18
“that keratinocyte necroptosis induced by Ripk1 deficiency was prevented by Ripk3 ablation in vivo [20].”
BackgroundNovel Discoveries in Immune Dysregulation in Inborn Errors of Immunity
Ren, A., Yin, W., Miller, H. E., Westerberg, L. S., Candotti, F., Park, C.-S., Lee, P. P. W., Gong, Q., Chen, Y., & Liu, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.725587 · Cited by 18
“RIPK1 can both mediate cell death and promote cell survival (86).”
BackgroundTargeting kinases that regulate programmed cell death: a new therapeutic strategy for breast cancer
Hong, Y. C., He, J., Deng, D., Liu, Q., Zu, X., & Shen, Y. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06367-9 · Cited by 20
Liu, J., Wang, J., Ren, J., Yang, Q., Zhan, W., Wang, M., Hao, L., & Yue, Y. (2021) · International Endodontic Journal · doi:10.1111/iej.13534 · Cited by 18
Ubiquitin-Mediated Regulation of Cell Death, Inflammation, and Defense of Homeostasis
Meier, P., Morris, O., & Broemer, M. (2015) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2015.07.015 · Cited by 18
“Proper regulation of RIPK1, and the ripoptosome, is critically important for normal development and physiology (Bonnet et al., 2011; Dannappel et al., 2014; Declercq et al., 2009; Dondelinger et al., 2013; Duprez et al., 2011; Ermolaeva et al., 2008; Green et al., 2011; O'Donnell et al., 2011; Oberst et al., 2011; Pas…”
BackgroundInfluentialEskandarpour, M., Nunn, M. A., Weston‐Davies, W., & Calder, V. L. (2021) · Cells · doi:10.3390/cells10020396 · Cited by 17
“receptors TNFR1 and TNFR2 can result in multiple downstream effects including inflammation, cell proliferation, apoptosis, tissue degeneration, host defence and necroptosis[77,78].”
BackgroundOzaka, S., Sonoda, A., Ariki, S., Kamiyama, N., Hidano, S., Sachi, N., Ito, K., Kudo, Y., Minata, M., Saechue, B., et al. (2021) · Genes to Cells · doi:10.1111/gtc.12888 · Cited by 16
Iliopoulou, L., & Kollias, G. A. (2021) · Mucosal Immunology · doi:10.1038/s41385-021-00433-3 · Cited by 19
Zeng, F., Wen, W., Cui, W., Zheng, W., Liu, Y., Sun, X., Hou, N., Ma, D., Yuan, Y., Shi, H., et al. (2018) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2018.10.015 · Cited by 16
Kaya, G. G., Schwarzer, R., Dannappel, M., Vlantis, K., Göbel, U., Kondylis, V., Nedospasov, S. A., & Pasparakis, M. (2025) · Immunity · doi:10.1016/j.immuni.2025.07.023 · Cited by 16
Self-citationTransient Inhibition of mTORC1 Signaling Ameliorates Irradiation-Induced Liver Damage
Yang, W., Shao, L., Zhu, S., Li, H., Zhang, X., Ding, C., Wu, X., Xu, R., Yue, M., Tang, J., et al. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00228 · Cited by 18
“If the dose is further increased to 60 Gy, the most effective dose for killing liver cancer, 76% of patients will die due to hepatic failure induced by irradiation (Ingold et al., 1965; Emami et al., 1991; Dawson et al., 2001).”
BackgroundHepatocyte Bcl-3 protects from death-receptor mediated apoptosis and subsequent acute liver failure
Gehrke, N., Wörns, M., Mann, A., Hövelmeyer, N., Waisman, A., Straub, B. K., Galle, P. R., & Schattenberg, J. M. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04946-y · Cited by 16
RIPK1 protects naive and regulatory T cells from TNFR1-induced apoptosis
Huysentruyt, J., Steels, W., Pérez, M., Verstraeten, B., Vadi, M., Divert, T., Flies, K., Takahashi, N., Lambrecht, B. N., Declercq, W., et al. (2024) · Cell Death and Differentiation · doi:10.1038/s41418-024-01301-w · Cited by 16
“…differentially expressed (DE)-genes in the cluster of CD4 + naive T cells (C1) of Ripk1 Δ CD4 mice compared to Ripk1 FL/FL littermates (left), Ripk1 Δ CD4 mice compared to Ripk1 Δ CD4 Casp8 Δ CD4 mice (middle) or Ripk1 Δ CD4 Casp8 Δ CD4 mice compared to Ripk1 FL/FL Casp8 FL/FL littermates (right).”
BackgroundcGAMP Promotes Germinal Center Formation and Production of IgA in Nasal-Associated Lymphoid Tissue
Takaki, H., Takashima, K., Oshiumi, H., Ainai, A., Suzuki, T., Hasegawa, H., Matsumoto, M., & Seya, T. (2017) · Medical Sciences · doi:10.3390/medsci5040035 · Cited by 16
Potential consequences of phototoxicity on cell function during live imaging of intestinal organoids
Yokoi, Y., Nakamura, R., Ohira, S., Takemi, S., Ayabe, T., & Nakamura, K. (2024) · PLoS ONE · doi:10.1371/journal.pone.0313213 · Cited by 15
The scaffold-dependent function of RIPK1 in dendritic cells promotes injury-induced colitis
Moriwaki, K., Park, C., Koyama, K., Balaji, S., Kita, K., Yagi, R., Komazawa‐Sakon, S., Semba, M., Asuka, T., Nakano, H., et al. (2021) · Mucosal Immunology · doi:10.1038/s41385-021-00446-y · Cited by 14
Zhao, Y., Zhang, J., Lu, H., Mao, Y., Qin, J., Wang, Y., Wang, X., Dai, Z., Wang, X., Yang, Z., et al. (2022) · Shock · doi:10.1097/shk.0000000000002006 · Cited by 15
“Under the stimulation of viral infection or inflammatory factors, necroptosis is the main form of AEC death (39,40).”
BackgroundPRMT5-mediated regulatory arginine methylation of RIPK3
Chauhan, C., Martínez‐Val, A., Niedenthal, R. K., Olsen, J. V., Kotlyarov, A., Bekker‐Jensen, S., Gaestel, M., & Menon, M. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01299-z · Cited by 14
“Studies using genetic models of RIPK1 deficiency has shown a kinase activityindependent scaffolding role for RIPK1 in preventing epithelial cell apoptosis and necroptosis [55].”
BackgroundBreaking bad: necroptosis in the pathogenesis of gastrointestinal diseases
Patankar, J. V., Bubeck, M., Acera, M. G., & Becker, C. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1203903 · Cited by 17
OTULIN protects the intestinal epithelium from apoptosis during inflammation and infection
Verboom, L., Anderson, C. J., Jans, M., Πέττα, Ι., Blancke, G., Martens, A., Sze, M., Hochepied, T., Ravichandran, K. S., Vereecke, L., et al. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06058-7 · Cited by 15
Cell death as an architect of adult skin stem cell niches
Lecomte, K., Toniolo, A., & Hoste, E. (2024) · Cell Death and Differentiation · doi:10.1038/s41418-024-01297-3 · Cited by 16
“Genetic ablation of key apoptotic mediators, such as caspase-8, FADD and RIPK1, in mouse KCs triggers KC necroptosis and severe skin in fl ammation [7 – 10] (Table 1).”
BackgroundInfluentialNecroptosis plays a role in TL1A-induced airway inflammation and barrier damage in asthma
Liu, X., Zhang, J., Zhang, D., Pan, Y., Zeng, R., Xu, C., Shi, S., Xu, J., Qi, Q., Dong, X., et al. (2024) · Respiratory Research · doi:10.1186/s12931-024-02900-4 · Cited by 15
Ullah, M. A., Rittchen, S., Li, J., Hasnain, S. Z., & Phipps, S. (2021) · Mucosal Immunology · doi:10.1038/s41385-021-00405-7 · Cited by 16
Kang, K., Lee, S., Piao, X., & Hur, G. M. (2019) · Archives of Pharmacal Research · doi:10.1007/s12272-018-01107-8 · Cited by 17
A proteomic perspective on TNF-mediated signalling and cell death
Tanzer, M. C. (2022) · Biochemical Society Transactions · doi:10.1042/bst20211114 · Cited by 15
Recent advances in targeting protein degradation for tumor immunotherapy
Li, S., Jin, Y., Wu, H., Yuan, H., & Zhao, J. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01765-4 · Cited by 14
“Additionally, RIPK1 inhibits necrop-totic signaling downstream of Toll-like receptor 3/4 (TLR3/4) and Z-DNA-binding protein 1 (ZBP1) via its scaffolding function, facilitating tumor immune evasion [127–132].”
Wang, S., Li, S., Li, Y., Jiang, Q., Li, X., Wang, Y., Han, J. J., Liu, Y., & Chen, Y. (2021) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.03.027 · Cited by 14
Excessive apoptosis of Rip1‐deficient T cells leads to premature aging
Wang, L., Zhang, X., Zhang, H., Lu, K., Li, M., Li, X., Ou, Y., Zhao, X., Wu, X., Wu, X., et al. (2023) · EMBO Reports · doi:10.15252/embr.202357925 · Cited by 14
“Since RIP1 serves as a key upstream regulator of necroptosis, apoptosis, and inflammation, and its death pattern is cell type-specific (Dannappel et al , 2014; Roderick et al , 2014; Lin et al , 2016; Newton et al , 2016; O’Donnell et al , 2018; Xu et al , 2018), we aimed to uncover the downstream…”
The Role of ALDH2 in Sepsis and the To-Be-Discovered Mechanisms
Pang, J., Zheng, Y., Han, Q., Zhang, Y., Sun, R., Wang, J., Xu, F., Zhang, Y., Ren, J. T., & Chen, Y. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-6260-6_10 · Cited by 14
Yanti, B., Mulyadi, M., Amin, M., Harapan, H., Mertaniasih, N. M., & Soetjipto, S. (2020) · BMC Research Notes · doi:10.1186/s13104-020-05256-2 · Cited by 15
RIPK1 signaling pathways: implications for autoimmune and neuroinflammatory diseases
Pajulas, A., Sims, J. T., Hanson, E. P., & Vendel, A. C. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1642593 · Cited by 13
Ma, X., Xie, J., Li, B., Shan, H., Jia, Z., Liu, W., Dong, Y., Han, S., & Jin, Q. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112761 · Cited by 13
Hair growth promotion by Necrostatin-1s
Zheng, M., Choi, N., Jang, Y., Kwak, D. E., Kim, Y. S., Kim, W.-S., Oh, S. H., & Sung, J.-H. (2020) · Scientific Reports · doi:10.1038/s41598-020-74796-1 · Cited by 13
Integrated stress response restricts macrophage necroptosis
Place, D. E., Samir, P., Malireddi, R. K. S., & Kanneganti, T. (2021) · Life Science Alliance · doi:10.26508/lsa.202101260 · Cited by 14
“…contributes to lethal developmental defects in mice lacking FADD, CASP8, and RIPK1, but mice lacking only RIPK3 or MLKL are viable, suggesting necroptosis plays an important role largely in cases where apoptosis is dysregulated (Dannappel et al, 2014; Dillon et al, 2014; Newton et al, 2016).”
BackgroundSakamoto, Y., Sasaki, K., Omatsu, M., Hamada, K., Nakanishi, Y., Itatani, Y., Kawada, K., Obama, K., Seno, H., & Iwaï, K. (2022) · The Journal of Pathology · doi:10.1002/path.6042 · Cited by 13
Yu, J., Hu, G., Cao, H., & Guo, X. (2022) · Animals · doi:10.3390/ani12243524 · Cited by 14
“The RIPK1 maintains epithelial homeostasis by inhibiting caspase 8-depedent apoptosis and necroptosis [49].”
BackgroundRegulation of RIP1‐Mediated necroptosis via necrostatin‐1 in periodontitis
Tan, L., Chan, W., Zhang, J., Wang, J., Wang, Z., Liu, J., Li, J., Liu, X., Wang, M., Hao, L., et al. (2023) · Journal of Periodontal Research · doi:10.1111/jre.13150 · Cited by 13
The 3-methyl-4-nitrophenol (PNMC) compromises airway epithelial barrier function
An, Y., Geng, X., Mo, L., Liu, J., Yang, L., Zhang, X., Liu, Z., Zhao, C., & Yang, P. (2018) · Toxicology · doi:10.1016/j.tox.2018.01.001 · Cited by 13
Dysregulation of Cell Death in Human Chronic InflammationPreprint
Li, Y., Klein, C., & Kotlarz, D. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a037036 · Cited by 15
The landscape of regulated cell death: It’s all downhill from here
Aufschnaiter, A., Oh, T., & Oberst, A. (2025) · Molecular Cell · doi:10.1016/j.molcel.2025.11.013 · Cited by 15
Notararigo, S., Varela, E., Otal, A., Cristobo, I., Antolı́n, M., Guarner, F., Prieto, A., & López, P. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.621280 · Cited by 12
IFNγ Causes Keratinocyte Necroptosis in Acute Graft-Versus-Host Disease
Freund, L., Oehrl, S., Schwingen, J., Haeberle, S., Döbel, T., Lee, P. D.-H., Meisel, S., Mihalceanu, S., Rußwurm, M., Luft, T., et al. (2023) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2023.02.025 · Cited by 13
Deng, X., Wang, L., Zhai, Y., Liu, Q., Du, F., Zhang, Y., Zhao, W., Wu, T., Tao, Y., Deng, J., et al. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-01113-x · Cited by 12
Roderick, J. E., Lim, S.-E., Suzuki, S., Ahmad, M. H., Selway, J., Suleiman, R., Karna, K. K., Lehman, J. W., O’Donnell, J. A., Castilla, L. H., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2309628121 · Cited by 12
“Ripk1 conditional mice ( Ripk1 fl/fl ) described previously (14) or Ripk1 fl/fl Ripk3 −/− mice were crossed with Vav - iCre mice (Jackson Laboratory 035670), Mlkl −/− mice (43) (gift of Warren Alexander), Zbp1 Za1a2/Za1a2 mice (16) (gift of Jan Rehwinkel), Infgr1 −/− (Jackson Laboratory 003288),…”
BackgroundSelf-citationStolzer, I., Ruder, B., Neurath, M. F., & Günther, C. (2021) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2021.151491 · Cited by 12
Gao, C., Deng, J., Zhang, H., Li, X., Gu, S., Zheng, M., Tang, M., Zhu, Y., Lin, X., Jin, J., et al. (2021) · Science Advances · doi:10.1126/sciadv.abh1756 · Cited by 12
The role of regulated necrosis in inflammation and ocular surface diseases
Guo, X.-X., Pu, Q., Hu, J., Chang, X., Li, A.-L., & Li, X. (2023) · Experimental Eye Research · doi:10.1016/j.exer.2023.109537 · Cited by 12
When Beauty Is Skin Deep: Regulation of the Wound Response by Caspase-8, RIPK3, and the Inflammasome
Vince, J. E. (2015) · Journal of Investigative Dermatology · doi:10.1038/jid.2015.185 · Cited by 12
“Alternatively, or at the same time, caspase-8 loss may stabilize a RIPK1/RIPK3 complex to induce TNF production and/or RIPK3/ MLKL-dependent NLRP3 inflammasome activation before necroptotic cell death.”
BackgroundInfluentialChico, J. F., Falk‐Paulsen, M., Luzius, A., Saggau, C., Ruder, B., Bolik, J., Schmidt‐Arras, D., Linkermann, A., Becker, C., Rosenstiel, P. C., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.24410 · Cited by 12
“Noteworthy, beyond acting as an upstream activator of RIPK3 [18-20], RIPK1 can also have an inhibiting role in RIPK3-dependent necroptosis [33-35].”
BackgroundGeneration of transgenic mice expressing a FRET biosensor, SMART, that responds to necroptosis
Murai, S., Takakura, K., Sumiyama, K., Moriwaki, K., Terai, K., Komazawa‐Sakon, S., Seki, T., Yamaguchi, Y., Mikami, T., Araki, K., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-04300-0 · Cited by 12
Necroptosis in immunity, tissue homeostasis, and cancer
Yin, J., Yu, Y., Huang, X., & Chan, F. K.-M. (2024) · Current Opinion in Immunology · doi:10.1016/j.coi.2024.102455 · Cited by 11
MLKL activity requires a splicing-regulated, druggable intramolecular interaction
Ros, U., Martinez-Osorio, V., Valiente, P. A., Abdelwahab, Y., Gojković, M., Shalaby, R., Zanna, S., Saggau, J., Wachsmuth, L., Nemade, H., et al. (2025) · Molecular Cell · doi:10.1016/j.molcel.2025.03.015 · Cited by 13
Self-citationMihaly, S. R., Sakamachi, Y., Ninomiya‐Tsuji, J., & Morioka, S. (2017) · Scientific Reports · doi:10.1038/s41598-017-03112-1 · Cited by 12
Role of RIP 1 in physiological enterocyte turnover in mouse small intestine via nonapoptotic death
Matsuoka, Y., & Tsujimoto, Y. (2014) · Genes to Cells · doi:10.1111/gtc.12193 · Cited by 11
Border Security: The Role of RIPK3 in Epithelium Homeostasis
Moriwaki, K., Balaji, S., & Chan, F. K.-M. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00070 · Cited by 11
Kolachala, V. L., Palle, S. K., Shen, M., Shenoi, A. N., Shayakhmetov, D. M., & Gupta, N. A. (2019) · Hepatology Communications · doi:10.1002/hep4.1352 · Cited by 11
“(27) demonstrated that RIPK1 signaling can also serve a prosurvival function and is essential for maintenance of the intestinal epithelial integrity in the gut.(28) Therefore, although RIP1 kinase is emerging as a multifunctional nexus regulating cellular prosurvival and prodeath decisions,(29) the exact molecular bas…”
BackgroundSaeki, Y., Okita, Y., Igashira-Oguro, E., Udagawa, C., Murata, A., Tanaka, T., Mukai, J., Miyazawa, K., Hoshida, Y., & Ohshima, S. (2021) · Clinical Rheumatology · doi:10.1007/s10067-021-05579-w · Cited by 12
RIPK1 downregulation enhances neutrophil extracellular traps in psoriasis
Meng, X., Guo, R., Fan, C., Li, Y., Liu, X., Chen, X., & Lu, L. (2022) · Advances in Dermatology and Allergology · doi:10.5114/ada.2022.113803 · Cited by 11
“RIPK3-MLKL-depedent and RIPK1-independent necroptosis contributed to skin inflammation [23].”
BackgroundMacrophage-endothelial cell crosstalk drives atherosclerotic plaque formation and progression
Zhang, C., Zhang, Y., Yu, Y., Zhou, M., Zhang, J., Fu, K., & Li, Y. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177879 · Cited by 10
RIPK1 is dispensable for cell death regulation in β-cells during hyperglycemia
Veli, Ö., Kaya, Ö., Varanda, A. B., Hildebrandt, X., Xiao, P., Estornes, Y., Poggenberg, M., Wang, Y., Pasparakis, M., Bertrand, M. J. M., et al. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.101988 · Cited by 10
“Since de fi ciency of RIPK1 induces apoptosis in certain cell types such as intestinal epithelial cells [29,30], we performed cl. Casp-3 staining to”
Self-citationMETTL3 restricts RIPK1-dependent cell death via the ATF3-cFLIP axis in the intestinal epithelium
Huang, M., Wang, X., Zhang, M., Liu, Y., & Chen, Y. (2024) · Cell Regeneration · doi:10.1186/s13619-024-00197-8 · Cited by 10
“Conversely, specific deficiency of Ripk1 in IECs leads to extensive apoptosis and necroptosis through its scaffold function but not kinase function (Dannappel et al. 2014; Takahashi et al. 2014).”
BackgroundReverse hierarchical DED assembly in the cFLIP-procaspase-8 and cFLIP-procaspase-8-FADD complexes
Yang, C., Tseng, Y.-C., Tu, Y.-F., Kuo, B.-J., Hsu, L.-C., Lien, C.-I., Lin, Y.-S., Wang, Y.-T., Lu, Y.-C., Su, T.-W., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-53306-1 · Cited by 10
“Additionally, a FADD-Casp-8-cFLIP-containg complex that inhibits TLR/TRIF or interferons (IFN)-initiated necroptosis via RIPK1 is crucial for postnatal development and maintaining epithelial homeostasis 41,42 .”
BackgroundWang, S., Liu, X., & Liu, Y. (2022) · Journal of Veterinary Science · doi:10.4142/jvs.22064 · Cited by 10
“RIPK1 is a key factor in necroptosis initiation; it combines with tumor necrosis factor receptor (TNFR) 1, TNFR1associated death domain (TRADD) protein, and TNFR-associated factor (TRAF)-2 through the death domain to form complex I, which can induce necroptosis through the formation of the RIPK1/RIPK3/mixed lineage ki…”
BackgroundCuproptosis patterns and tumor microenvironment in endometrial cancer
Chen, J., Wang, G., Luo, X., Zhang, J., & Zhang, Y. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.1001374 · Cited by 10
“Apoptosis, necroptosis, pyroptosis, ferroptosis, and other types of cell death, among others, were all connected to tumor development, metastasis, and immune treatment, according to earlier research (Andersen et al., 2005; Dannappel et al., 2014; Karki and Kanneganti, 2019; Lei et al., 2022).”
ResultRengaraj, D., Truong, A. D., Lee, S. H., Lillehoj, H. S., & Hong, Y. H. (2015) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2015.12.010 · Cited by 10
Metadata
- Authors
- Dannappel, M., Vlantis, K., Kumari, S., Polykratis, A., Kim, C., Wachsmuth, L., Eftychi, C., Lin, J., Corona, T., Hermance, N., Zelic, M., Kirsch, P., Basic, M., Bleich, A., Kelliher, M., & Pasparakis, M.
- Affiliations
- University of Cologne (DE)
- University of Massachusetts Chan Medical School (US)
- Universität Ulm (DE)
- Medizinische Hochschule Hannover (DE)
- Corresponding author
- Pasparakis, Manolis
- ORCID
- Venue
- Nature
- Published
- 2014-08-17
- Volume
- 513
- Issue
- 7516
- Pages
- 90-94
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4206266
- OpenAlex
- W1985231277
- Cited by
- 534
- References
- 47
- Citations by year
- 2026: 21 · 2025: 33 · 2024: 46 · 2023: 36 · 2022: 56 · 2021: 47 · 2020: 47 · 2019: 49 · 2018: 44 · 2017: 33 · 2016: 59 · 2015: 49 · 2014: 14
- FWCI
- 21.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI075118, T32AI095213)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- RIPK1, necroptosis, apoptosis, epithelial homeostasis, FADD, caspase-8, RIPK3, intestinal epithelium, skin inflammation, keratinocytes, TNFR1, barrier tissues, inflammation, programmed cell death, Paneth cells, goblet cells, villous atrophy, intestinal inflammation
- MeSH terms
- Animals, Cell Survival, Epithelial Cells, Female, Homeostasis, Inflammation, Intestinal Mucosa, Intestines, Male, Necrosis, Skin, Keratinocytes, Apoptosis, Mice, Knockout, Paneth Cells, Receptors, Tumor Necrosis Factor, Type I, Mice, Caspase 8, Fas-Associated Death Domain Protein, Receptor-Interacting Protein Serine-Threonine Kinases, Myeloid Differentiation Factor 88
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
