The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Complementary roles of Fas-associated death domain (FADD) and receptor interacting protein kinase-3 (RIPK3) in T-cell homeostasis and antiviral immunity
Open accessAbstract
Caspase-8 (casp8) is required for extrinsic apoptosis, and mice deficient in casp8 fail to develop and die in utero while ultimately failing to maintain the proliferation of T cells, B cells, and a host of other cell types. Paradoxically, these failures are not caused by a defect in apoptosis, but by a presumed proliferative function of this protease. Indeed, following mitogenic stimulation, T cells lacking casp8 or its adaptor protein FADD (Fas-associated death domain protein) develop a hyperautophagic morphology, and die a programmed necrosis-like death process termed necroptosis. Recent studies have demonstrated that receptor-interacting protein kinases (RIPKs) RIPK1 and RIPK3 together facilitate TNF-induced necroptosis, but the precise role of RIPKs in the demise of T cells lacking FADD or casp8 activity is unknown. Here we demonstrate that RIPK3 and FADD have opposing and complementary roles in promoting T-cell clonal expansion and homeostasis. We show that the defective proliferation of T cells bearing an interfering form of FADD (FADDdd) is rescued by crossing with RIPK3 −/− mice, although such rescue ultimately leads to lymphadenopathy. Enhanced recovery of these double-mutant T cells following stimulation demonstrates that FADD, casp8, and RIPK3 are all essential for clonal expansion, contraction, and antiviral responses. Finally, we demonstrate that caspase-mediated cleavage of RIPK1-containing necrosis inducing complexes (necrosomes) is sufficient to prevent necroptosis in the face of death receptor signaling. These studies highlight the “two-faced” nature of casp8 activity, promoting clonal expansion in some situations and apoptotic demise in others.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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
“Moreover, the proliferative defects of Casp8−/− or Fadd−/− T cells can be rescued by the administration of the RIPK1 inhibitor Nec-1 or the concomitant ablation of Ripk3 [489].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [489]
Citations
Cites
Death Receptors: Signaling and Modulation
Ashkenazi, A., & Dixit, V. M. (1998) · Science · doi:10.1126/science.281.5381.1305 · Cited by 5,866
T cell receptor antagonist peptides induce positive selection.
Hogquist, K., Jameson, S., Heath, W., Howard, J. L., Bevan, M., & Carbone, F. (1994) · Cell · doi:10.1016/0092-8674(94)90169-4 · Cited by 3,252
Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
Degterev, A., Huang, Z., Boyce, M., Li, Y., Jagtap, P., Mizushima, N., Cuny, G. D., Mitchison, T. J., Moskowitz, M. A., & Yuan, J. (2005) · Nature Chemical Biology · doi:10.1038/nchembio711 · Cited by 3,068
Cho, Y., Challa, S., Moquin, D., Genga, R., Ray, T. D., Guildford, M., & Chan, F. K.-M. (2009) · Cell · doi:10.1016/j.cell.2009.05.037 · Cited by 2,435
Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α
He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., & Wang, X. (2009) · Cell · doi:10.1016/j.cell.2009.05.021 · Cited by 2,214
Holler, N., Zaru, R., Micheau, O., Thome, M., Attinger, A., Valitutti, S., Bodmer, J.-L., Schneider, P., Seed, B., & Tschopp, J. (2000) · Nature Immunology · doi:10.1038/82732 · Cited by 1,987
RIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis
Zhang, D.-W., Shao, J., Lin, J., Zhang, N., Lu, B.-J., Lin, S.-C., Dong, M.-Q., & Han, J. (2009) · Science · doi:10.1126/science.1172308 · Cited by 1,931
The Death Domain Kinase RIP Mediates the TNF-Induced NF-κB Signal
Kelliher, M. A., Grimm, S., Ishida, Y., Kuo, F., Stanger, B. Z., & Leder, P. (1998) · Immunity · doi:10.1016/s1074-7613(00)80535-x · Cited by 1,102
RIP3 mediates the embryonic lethality of caspase-8-deficient mice
Kaiser, W. J., Upton, J. W., Long, A. B., Livingston-Rosanoff, D., Daley-Bauer, L. P., Hakem, R., Caspary, T., & Mocarski, E. S. (2011) · Nature · doi:10.1038/nature09857 · Cited by 1,057
Hitomi, J., Christofferson, D. E., Ng, A., Yao, J., Degterev, A., Xavier, R. J., & Yuan, J. (2008) · Cell · doi:10.1016/j.cell.2008.10.044 · Cited by 989
Cited by
Sorted by citations
Items 101–123 of 123
Hutchinson, R. A., Coleman, H. G., Gately, K. A., Young, V., Nicholson, S. A., Cummins, R., Kay, E. W., Hynes, S. O., Dunne, P. D., Senevirathne, S., et al. (2017) · Cell Death Discovery · doi:10.1038/cddiscovery.2017.50 · Cited by 5
Zhang, X., Huo, L., Song, L., Hu, Z., Wang, X., Han, Y., Wang, Y., Xu, P., Zhang, J., & Hua, Z. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02038 · Cited by 4
Inhibition of receptor interacting protein kinase-1 (RIPK1) in the treatment of murine lupus
Peng, L., Wang, P., Xu, X., Chen, D., Xu, F., Yang, F., Yang, S., Xia, H., Liu, Z., & Qin, W. (2024) · Lupus Science & Medicine · doi:10.1136/lupus-2024-001146 · Cited by 3
He, J., Wang, Y.-Q., Feng, J., Li, J., Xu, L., Li, X., Wang, W., Huan, X., Jiang, Y., Yu, B., et al. (2012) · Acta Pharmacologica Sinica · doi:10.1038/aps.2012.1 · Cited by 2
Necroptosis, a Potential Therapeutic Target for Neurological Disorders
Chen, J., Kostrzewa, R. M., & Xu, X. (2014) · Springer eBooks · doi:10.1007/978-1-4614-5836-4_166 · Cited by 2
Seminars in Cell & Developmental Biology
Zhou, W., & Yuan, J. (2014) · Cited by 2
Ars moriendi: Proteases as sculptors of cellular suicide
Heib, M., Weiß, J., Saggau, C., Hoyer, J., Chico, J. F., Voigt, S., & Adam, D. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2021.119191 · Cited by 2
NOX1, Reactive Oxygen Species, JNK, and Necrotic Cell Death
Morgan, M. J., & Kim, Y. (2014) · Springer eBooks · doi:10.1007/978-1-4614-8220-8_8 · Cited by 1
TRAF6 Affects RAC1 Expression and Apoptosis in SK-Hep1 Cells
Zhang, S., Qian, C., Liu, X., Piao, S., & Jin, X. (2018) · Chinese Medicine · doi:10.4236/cm.2018.94011 · Cited by 1
Manipulation of host cell death and innate immune signaling pathways by Coxsackievirus B3
Harris, K. G. (2015) · D-Scholarship@Pitt (University of Pittsburgh)
Dead if You Do, Dead if You Don’t: How Caspase-8 Causes and Prevents Cell Death
Oberst, A. (2014) · Springer eBooks · doi:10.1007/978-1-4614-8220-8_6
Programmed Necrosis in Immunity and Inflammatory Diseases
Moriwaki, K., & Chan, F. K.-M. (2014) · Springer eBooks · doi:10.1007/978-1-4614-8220-8_10
The Paradoxical Roles of Cell Death Pathways in Immune Cells
McComb, S. (2013) · uO Research (University of Ottawa) · doi:10.20381/ruor-3097
Effect of IRAK1 on Apoptosis and Necroptosis of Hepatoma Cell Line SK-Hep1
Pan, Z., Zhang, X., Qian, C., Liu, X., & Jin, X. (2019) · Chinese Medicine · doi:10.4236/cm.2019.101003
Modulação da resposta anti-tumoral por agentes infecciosos modificados geneticamente
Rana, A. (2020) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2020.tde-18122019-102800
McDermott, M., & Jarosz-Griffiths, H. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.727137491.793555154
Elucidating the Molecular Mechanism of CYLD-Mediated Necrosis: A Dissertation
Moquin, D. (2013) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/m2ww39
He, L., Zhan, F., Lu, L., Zhang, X., & Wu, J. (2024) · Figshare · doi:10.6084/m9.figshare.26601958
He, L., Zhan, F., Lu, L., Zhang, X., & Wu, J. (2024) · Figshare · doi:10.6084/m9.figshare.26601952
He, L., Zhan, F., Lu, L., Zhang, X., & Wu, J. (2024) · Figshare · doi:10.6084/m9.figshare.26601955
Deciphering the role of the death receptor Fas/CD95 in T cell co-stimulation
Miloro, G. (2020) · theses.fr (ABES) · doi:10.70675/3417ba39z26acz4dd9zb559zd7e545ef2294
Sex-specific molecular signatures in persistent pain after whiplash injury: an exploratory analysis
Fundaun, J., Ridehalgh, C., Dilley, A., Schmid, A. B., & Baskozos, G. (2026) · PAIN Reports · doi:10.1097/pr9.0000000000001479
Metadata
- Authors
- Lu, J. V., Weist, B. M., van Raam, B. J., Marro, B. S., Nguyen, L. V., Srinivas, P., Bell, B. D., Luhrs, K. A., Lane, T. E., Salvesen, G. S., & Walsh, C. M.
- Affiliations
- University of California, Irvine (US)
- Sanford–Burnham Medical Research Institute, La Jolla, CA 92037
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-08-29
- Volume
- 108
- Issue
- 37
- Pages
- 15312-15317
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3174674
- OpenAlex
- W2089868528
- Cited by
- 122
- References
- 40
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 10 · 2019: 10 · 2018: 6 · 2017: 5 · 2016: 13 · 2015: 17 · 2014: 14 · 2013: 10 · 2012: 11
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 69381, P01CA069381, P30CA062203, T32CA009054)
- National Institute of Allergy and Infectious Diseases (R01AI063419, AI50506, R01AI050506, AI63419)
- National Institute of Neurological Disorders and Stroke (NS41249, R01NS041249)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- FADD, RIPK3, caspase-8, T cell homeostasis, T cell clonal expansion, necroptosis, necrosome, RIPK1, antiviral immunity, death receptor signaling, apoptosis, lymphadenopathy, T cell proliferation
- MeSH terms
- Animals, Cell Survival, Crosses, Genetic, Female, Murine hepatitis virus, Hepatitis, Viral, Animal, Homeostasis, Immunity, Male, CD8-Positive T-Lymphocytes, Cell Proliferation, Mice, Fas-Associated Death Domain Protein, Receptor-Interacting Protein Serine-Threonine Kinases
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
