RETRACTED ARTICLE: Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells
Open accessAbstract
Defects in clearance of dying cells have been proposed to underlie the pathogenesis of systemic lupus erythematosus (SLE). Mice lacking molecules associated with dying cell clearance develop SLE-like disease, and phagocytes from patients with SLE often display defective clearance and increased inflammatory cytokine production when exposed to dying cells in vitro. Previously, we and others described a form of noncanonical autophagy known as LC3-associated phagocytosis (LAP), in which phagosomes containing engulfed particles, including dying cells, recruit elements of the autophagy pathway to facilitate maturation of phagosomes and digestion of their contents. Genome-wide association studies have identified polymorphisms in the Atg5 (ref. 8) and possibly Atg7 (ref. 9) genes, involved in both canonical autophagy and LAP, as markers of a predisposition for SLE. Here we describe the consequences of defective LAP in vivo. Mice lacking any of several components of the LAP pathway show increased serum levels of inflammatory cytokines and autoantibodies, glomerular immune complex deposition, and evidence of kidney damage. When dying cells are injected into LAP-deficient mice, they are engulfed but not efficiently degraded and trigger acute elevation of pro-inflammatory cytokines but not anti-inflammatory interleukin (IL)-10. Repeated injection of dying cells into LAP-deficient, but not LAP-sufficient, mice accelerated the development of SLE-like disease, including increased serum levels of autoantibodies. By contrast, mice deficient in genes required for canonical autophagy but not LAP do not display defective dying cell clearance, inflammatory cytokine production, or SLE-like disease, and, like wild-type mice, produce IL-10 in response to dying cells. Therefore, defects in LAP, rather than canonical autophagy, can cause SLE-like phenomena, and may contribute to the pathogenesis of SLE.
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Rubicon is an inhibitor of canonical autophagy and a key component of a non-canonical function of autophagy proteins that modulates inflammatory immune activation.
“Rubicon has been shown to be an inhibitor of canonical autophagy (Matsunaga et al., 2009) and a key component of a non-canonical function of autophagy proteins that modulates inflammatory immune activation (Cunha et al., 2018; Martinez et al., 2016).”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Martinez et al., 2016
LAP has a vital role in regulating inflammatory immune responses.
“Since we have previously shown a vital role for LAP in regulating inflammatory immune responses (Martinez et al., 2016), we hypothesized that defective LANDO may have a similar effect.”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Martinez et al., 2016
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2 retracted
Martinez, J., Malireddi, R. K. S., Lu, Q., Cunha, L. D., Pelletier, S., Gingras, S., Orchard, R., Guan, J.-L., Tan, H., Peng, J., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3192 · Cited by 758 · see citing works
Self-citationRetractedMartinez, J., Almendinger, J., Oberst, A., Ness, R., Dillon, C. P., Fitzgerald, P., Hengartner, M. O., & Green, D. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113421108 · Cited by 655 · see citing works
Self-citationRetractedAutophagy and Viruses: Adversaries or Allies?
Dong, X., & Levine, B. (2013) · Journal of Innate Immunity · doi:10.1159/000346388 · Cited by 4,441 · see citing works
Antimicrobial Autophagy: A Conserved Innate Immune Response in Drosophila
Moy, R. H., & Cherry, S. R. (2013) · Journal of Innate Immunity · doi:10.1159/000350326 · Cited by 3,549 · see citing works
Conditional gene targeting in macrophages and granulocytes using LysMcre mice
Clausen, B. E., Burkhardt, C., Reith, W., Renkawitz, R., & Förster, I. (1999) · Transgenic Research · doi:10.1023/a:1008942828960 · Cited by 2,143 · see citing works
Hampe, J., Franke, A., Rosenstiel, P. C., Till, A., Teuber, M., Huse, K., Albrecht, M., Gabriele Mayr, B., Vega, F. M. D. L., Briggs, J. C., et al. (2006) · Nature Genetics · doi:10.1038/ng1954 · Cited by 1,899 · see citing works
Autophagy in mammalian development and differentiation
Mizushima, N., & Levine, B. (2010) · Nature Cell Biology · doi:10.1038/ncb0910-823 · Cited by 1,555 · see citing works
Murine Models of Systemic Lupus Erythematosus
Theofilopoulos, A. N., & Dixon, F. J. (1985) · Advances in immunology · doi:10.1016/s0065-2776(08)60342-9 · Cited by 1,553 · see citing works
Shi, C.-S., Shenderov, K., Huang, N.-N., Kabat, J., Abu-Asab, M., Fitzgerald, K. A., Sher, A., & Kehrl, J. H. (2012) · Nature Immunology · doi:10.1038/ni.2215 · Cited by 1,367 · see citing works
Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis
Sanjuan, M. A., Dillon, C. P., Tait, S. W. G., Moshiach, S., Dorsey, F., Connell, S., Komatsu, M., Tanaka, K., Cleveland, J. L., Withoff, S., et al. (2007) · Nature · doi:10.1038/nature06421 · Cited by 1,347 · see citing works
Self-citationMatsunaga, K., Saitoh, T., Tabata, K., Omori, H., Satoh, T., Kurotori, N., Maejima, I., Shirahama-Noda, K., Ichimura, T., Isobe, T., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1846 · Cited by 1,235 · see citing works
Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums
Ravichandran, K. S. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20101157 · Cited by 547 · see citing works
Polygenic control of susceptibility to murine systemic lupus erythematosus
Morel, L. M., Rudofsky, U. H., Longmate, J., Schiffenbauer, J., & Wakeland, E. K. (1994) · Immunity · doi:10.1016/1074-7613(94)90100-7 · Cited by 471 · see citing works
Florey, O., Kim, S. E., Sandoval, C. P., Haynes, C. M., & Overholtzer, M. (2011) · Nature Cell Biology · doi:10.1038/ncb2363 · Cited by 459 · see citing works
Murine Models of Systemic Lupus Erythematosus
Perry, D. J., Sang, A. L., Yin, Y., Zheng, Y.-Y., & Morel, L. M. (2011) · BioMed Research International · doi:10.1155/2011/271694 · Cited by 379 · see citing works
Henault, J., Martinez, J., Riggs, J. M., Tian, J., Mehta, P., Clarke, L., Sasai, M., Latz, E., Brinkmann, M. M., Iwasaki, A., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.09.014 · Cited by 348 · see citing works
Self-citationNoncanonical autophagy promotes the visual cycle
Kim, J.-Y., Zhao, H., Martinez, J., Doggett, T. A., Kolesnikov, A. V., Tang, P. H., Ablonczy, Z., Chan, C.-C., Zhou, Z., Green, D. R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.012 · Cited by 347 · see citing works
Self-citationThe interferon signature in autoimmune diseases
Rönnblom, L., & Eloranta, M. (2012) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e32835c7e32 · Cited by 294 · see citing works
Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation
Juncadella, I. J., Kadl, A., Sharma, A. K., Shim, Y. M., Hochreiter, A. E., Borish, L., & Ravichandran, K. S. (2012) · Nature · doi:10.1038/nature11714 · Cited by 287 · see citing works
Serum interleukin 10 titers in systemic lupus erythematosus reflect disease activity
Houssiau, F., Lefebvre, C., Berghe, M. V., Lambert, M., Devogelaer, J.-P., & Renauld, J. (1995) · Lupus · doi:10.1177/096120339500400510 · Cited by 281 · see citing works
Autophagy is activated in systemic lupus erythematosus and required for plasmablast development
Clarke, A. J., Ellinghaus, U., Cortini, A., Stranks, A., Simon, A. K., Botto, M., & Vyse, T. J. (2015) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-204343 · Cited by 252 · see citing works
NADPH Oxidase Inhibits the Pathogenesis of Systemic Lupus Erythematosus
Campbell, A. M., Kashgarian, M. J., & Shlomchik, M. J. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004801 · Cited by 246 · see citing works
Zhou, S., Lu, X., Lv, J., Yang, H.-Z., qin, L. X., Zhao, M., Su, Y., Li, Z., & Zhang, H. (2011) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2010.140111 · Cited by 240 · see citing works
Chronic granulomatous disease as a risk factor for autoimmune disease
Ravin, S. S. D., Naumann, N., Cowen, E. W., Friend, J. C., Hilligoss, D. M., Marquesen, M., Balow, J. E., Barron, K. S., Turner, M. L. C., Gallin, J. I., et al. (2008) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2008.07.050 · Cited by 231 · see citing works
Yin, Z., Bahtiyar, G., Zhang, N., Liu, L., Zhu, P., Robert, M., McNiff, J. M., Madaio, M. P., & Craft, J. E. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.4.2148 · Cited by 228 · see citing works
Rodriguez‐Manzanet, R., Sanjuán, M. A. F., Wu, H. Y., Quintana, F. J., Xiao, S., Anderson, A. C., Weiner, H. L., Green, D. R., & Kuchroo, V. K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910359107 · Cited by 182 · see citing works
Self-citationB Cell-Derived IL-10 Does Not Regulate Spontaneous Systemic Autoimmunity in MRL.Faslpr Mice
Teichmann, L. L., Kashgarian, M. J., Weaver, C. T., Roers, A., Müller, W., & Shlomchik, M. J. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1102456 · Cited by 94 · see citing works
IL-10 regulation of lupus in the NZM2410 murine model
Blenman, K., Duan, B., Xu, Z., Wan, S., Atkinson, M. A., Flotte, T. R., Croker, B. P., & Morel, L. M. (2006) · Laboratory Investigation · doi:10.1038/labinvest.3700468 · Cited by 82 · see citing works
FIP200, a key signaling node to coordinately regulate various cellular processes
Gan, B., & Guan, J.-L. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2007.10.021 · Cited by 67 · see citing works
Ma, L., Chan, K., Trendell-Smith, N. J., Wu, A., Tian, L., Lam, A. C., Chan, A. K. F., Lo, C., Chik, S. C. C., Ko, K., et al. (2005) · European Journal of Immunology · doi:10.1002/eji.200535192 · Cited by 59 · see citing works
Influence of Atg5 Mutation in SLE Depends on Functional IL-10 Genotype
López, P., Alonso‐Perez, E., Rodríguez‐Carrio, J., & Suárez, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078756 · Cited by 51 · see citing works
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Biological Functions of Autophagy Genes: A Disease Perspective
Levine, B., & Kroemer, G. (2019) · Cell · doi:10.1016/j.cell.2018.09.048 · Cited by 2,832 · see citing works
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Self-citationThe cGAS–STING pathway as a therapeutic target in inflammatory diseases
Decout, A., Katz, J. D., Venkatraman, S., & Ablasser, A. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00524-z · Cited by 2,309 · see citing works
Molecular definitions of autophagy and related processes
Galluzzi, L., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cecconi, F., Choi, A. M., Chu, C. T., Codogno, P., Colombo, M. I., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201796697 · Cited by 1,646 · see citing works
Self-citationAutophagy in major human diseases
Klionsky, D. J., Petroni, G., Amaravadi, R. K., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cadwell, K., Cecconi, F., Choi, A. M. K., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108863 · Cited by 1,585 · see citing works
Self-citationMizushima, N., & Levine, B. (2020) · New England Journal of Medicine · doi:10.1056/nejmra2022774 · Cited by 1,140 · see citing works
The clearance of dead cells by efferocytosis
Boada-Romero, E., Martinez, J., Heckmann, B. L., & Green, D. R. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0232-1 · Cited by 893 · see citing works
Self-citationAutophagy-Independent Functions of the Autophagy Machinery
Galluzzi, L., & Green, D. R. (2019) · Cell · doi:10.1016/j.cell.2019.05.026 · Cited by 863 · see citing works
“Of note, neurodegeneration imposed by Ulk1/Ulk2 co-deletion is also accompanied by defective axonal pathfinding affecting multiple areas of the forebrain, and similar alterations cannot be recapitulated by the brain-specific deletion of Atg7 or Rb1cc1 (Wang et al., 2018).”
BackgroundInfluentialSelf-citationAutophagy in inflammation, infection, and immunometabolism
Deretic, V. (2021) · Immunity · doi:10.1016/j.immuni.2021.01.018 · Cited by 862 · see citing works
Autophagy and mitophagy in cardiovascular disease
Bravo-San Pedro, J. M., Kroemer, G., & Galluzzi, L. (2017) · Circulation Research · doi:10.1161/circresaha.117.311082 · Cited by 843 · see citing works
Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles
Galluzzi, L., Bravo-San Pedro, J. M., Levine, B., Green, D. R., & Kroemer, G. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.22 · Cited by 842 · see citing works
Self-citationLC3/GABARAP family proteins: autophagy‐(un)related functions
Schaaf, M. B. E., Keulers, T. G., Vooijs, M., & Rouschop, K. M. A. (2016) · The FASEB Journal · doi:10.1096/fj.201600698r · Cited by 652 · see citing works
The multiple pathways to autoimmunity
Theofilopoulos, A. N., Kono, D. H., & Baccala, R. (2017) · Nature Immunology · doi:10.1038/ni.3731 · Cited by 590 · see citing works
Linking cellular stress responses to systemic homeostasis
Galluzzi, L., Yamazaki, T., & Kroemer, G. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0068-0 · Cited by 529 · see citing works
Heckmann, B. L., Teubner, B. J. W., Tummers, B., Boada-Romero, E., Harris, L., Yang, M., Guy, C. S., Zakharenko, S. S., & Green, D. R. (2019) · Cell · doi:10.1016/j.cell.2019.05.056 · Cited by 503 · see citing works
“Since we have previously shown a vital role for LAP in regulating inflammatory immune responses (Martinez et al., 2016), we hypothesized that defective LANDO may have a similar effect.”
Self-citationCrosstalk between autophagy and inflammatory signalling pathways: balancing defence and homeostasis
Cadwell, K. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.100 · Cited by 478 · see citing works
Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective
Moulton, V. R., Suárez‐Fueyo, A., Meidan, E., Li, H., Mizui, M., & Tsokos, G. C. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.05.006 · Cited by 478 · see citing works
Efferocytosis Signaling in the Regulation of Macrophage Inflammatory Responses
Elliott, M. R., Koster, K. M., & Murphy, P. S. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601520 · Cited by 440 · see citing works
Autophagy in tumour immunity and therapy
Xia, H., Green, D. R., & Zou, W. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00344-2 · Cited by 411 · see citing works
Self-citationLiving on the Edge: Efferocytosis at the Interface of Homeostasis and Pathology
Morioka, S., Maueröder, C., & Ravichandran, K. S. (2019) · Immunity · doi:10.1016/j.immuni.2019.04.018 · Cited by 391 · see citing works
Matsuzawa, Y., Hwang, S., & Cadwell, K. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053253 · Cited by 378 · see citing works
Mitochondrial fission promotes the continued clearance of apoptotic cells by macrophages
Wang, Y., Subramanian, M., Yurdagul, A., Barbosa-Lorenzi, V. C., Cai, B., de Juan-Sanz, J., Ryan, T. A., Nomura, M., Maxfield, F. R., & Tabas, I. (2017) · Cell · doi:10.1016/j.cell.2017.08.041 · Cited by 364 · see citing works
Constitutive immune mechanisms: mediators of host defence and immune regulation
Paludan, S. R., Pradeu, T., Masters, S. L., & Mogensen, T. H. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-0391-5 · Cited by 363 · see citing works
Role of lysosomes in physiological activities, diseases, and therapy
Zhang, Z., Yue, P., Lu, T., Wang, Y., Wei, Y., & Wei, X. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01087-1 · Cited by 364 · see citing works
Autophagy in the renewal, differentiation and homeostasis of immune cells
Clarke, A. J., & Simon, A. K. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-018-0095-2 · Cited by 361 · see citing works
Hydroxychloroquine in systemic lupus erythematosus (SLE)
Ponticelli, C. E., & Moroni, G. L. (2016) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2017.1269168 · Cited by 345 · see citing works
LC3-Associated Phagocytosis in Myeloid Cells Promotes Tumor Immune Tolerance
Cunha, L. D., Yang, M., Carter, R., Guy, C., Harris, L., Crawford, J. C., Quarato, G., Boada-Romero, E., Kalkavan, H., Johnson, M. D. L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.061 · Cited by 334 · see citing works
Self-citationAutophagy and Microglia: Novel Partners in Neurodegeneration and Aging
Plaza-Zabala, A., Sierra-Torre, V., & Sierra, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18030598 · Cited by 323 · see citing works
Microglia in Alzheimer’s disease: pathogenesis, mechanisms, and therapeutic potentials
Miao, J., Ma, H., Yang, Y., Liao, Y., Lin, C., Zheng, J., Yu, M., & Lan, J. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1201982 · Cited by 293 · see citing works
Fletcher, K., Ulferts, R., Jacquin, É., Veith, T., Gammoh, N., Arasteh, J. M., Mayer, U., Carding, S. R., Wileman, T. E., Beale, R. C. L., et al. (2018) · The EMBO Journal · doi:10.15252/embj.201797840 · Cited by 292 · see citing works
Patterns, Receptors, and Signals: Regulation of Phagosome Maturation
Pauwels, A.-M., Trost, M., Beyaert, R., & Hoffmann, E. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.03.006 · Cited by 264 · see citing works
LC3-Associated Phagocytosis and Inflammation
Heckmann, B. L., Boada-Romero, E., Cunha, L. D., Magne, J., & Green, D. R. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.08.012 · Cited by 276 · see citing works
Self-citationLC3-associated phagocytosis at a glance
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Self-citationAutophagy and Macrophage Functions: Inflammatory Response and Phagocytosis
Wu, M.-Y., & Lu, J. (2019) · Cells · doi:10.3390/cells9010070 · Cited by 266 · see citing works
Wang, W., Liu, W., Fidler, T., Wang, Y., Tang, Y., Woods, B., Welch, C., Cai, B., Silvestre-Roig, C., Ai, D., et al. (2018) · Circulation Research · doi:10.1161/circresaha.118.313283 · Cited by 262 · see citing works
Tissue-resident macrophages are locally programmed for silent clearance of apoptotic cells
Roberts, A. W., Lee, B. L., Deguine, J., John, S., Shlomchik, M. J., & Barton, G. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.10.006 · Cited by 261 · see citing works
Jia, D., Chen, S., Bai, P., Luo, C., Liu, J., Sun, A., & Ge, J. (2022) · Circulation · doi:10.1161/circulationaha.121.057549 · Cited by 245 · see citing works
Autophagosome Maturation and Fusion
Reggiori, F., & Ungermann, C. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.01.002 · Cited by 235 · see citing works
Wang, S., Li, H., Yuan, M., Fan, H., & Cai, Z. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.1015500 · Cited by 229 · see citing works
Autophagy and kidney inflammation
Kimura, T., Isaka, Y., & Yoshimori, T. (2017) · Autophagy · doi:10.1080/15548627.2017.1309485 · Cited by 226 · see citing works
Targeting lysosomes in human disease: from basic research to clinical applications
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Autophagy as a modulator of cell death machinery
Noguchi, M., Hirata, N., Tanaka, T., Suizu, F., Nakajima, H., & Chiorini, J. A. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2724-5 · Cited by 215 · see citing works
Non-canonical autophagy drives alternative ATG8 conjugation to phosphatidylserine
Durgan, J., Lystad, A. H., Sloan, K., Carlsson, S. R., Wilson, M. I., Marcassa, E., Ulferts, R., Webster, J. A., Lopez‐Clavijo, A. F., Wakelam, M. J. O., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.03.020 · Cited by 216 · see citing works
DNA Sensing in the Innate Immune Response
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Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis
Mistry, P., & Kaplan, M. J. (2016) · Clinical Immunology · doi:10.1016/j.clim.2016.08.010 · Cited by 207 · see citing works
Beyond autophagy: LC3-associated phagocytosis and endocytosis
Peña-Martinez, C., Rickman, A. D., & Heckmann, B. L. (2022) · Science Advances · doi:10.1126/sciadv.abn1702 · Cited by 212 · see citing works
Activation and targeting of ATG8 protein lipidation
Martens, S., & Fracchiolla, D. (2020) · Cell Discovery · doi:10.1038/s41421-020-0155-1 · Cited by 206 · see citing works
Flipping the dogma – phosphatidylserine in non-apoptotic cell death
Shlomovitz, I., Speir, M., & Gerlic, M. (2019) · Cell Communication and Signaling · doi:10.1186/s12964-019-0437-0 · Cited by 184 · see citing works
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Hooper, K. M., Jacquin, É., Li, T., Goodwin, J. M., Brumell, J. H., Durgan, J., & Florey, O. (2022) · The Journal of Cell Biology · doi:10.1083/jcb.202105112 · Cited by 188 · see citing works
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Zhao, J. H., Ma, J., Deng, Y., Kelly, J. A., Kim, K.-W., Bang, S., Lee, H., Li, Q., Wakeland, E. K., Qiu, R., et al. (2017) · Nature Genetics · doi:10.1038/ng.3782 · Cited by 184 · see citing works
Self-citationDurgan, J., & Florey, O. (2022) · Science Advances · doi:10.1126/sciadv.abo1274 · Cited by 176 · see citing works
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Xu, Y., Propson, N. E., Du, S., Xiong, W., & Zheng, H. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2023418118 · Cited by 171 · see citing works
Jacquin, É., Leclerc‐Mercier, S., Judon, C., Blanchard, E., Fraitag, S., & Florey, O. (2017) · Autophagy · doi:10.1080/15548627.2017.1287653 · Cited by 166 · see citing works
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Ceccariglia, S., Cargnoni, A., Silini, A. R., & Parolini, O. (2019) · Autophagy · doi:10.1080/15548627.2019.1630223 · Cited by 162 · see citing works
The pathological features of regulated necrosis
Tonnus, W., Meyer, C., Paliege, A., Belavgeni, A., von Mäßenhausen, A., Bornstein, S. R., Hugo, C., Becker, J. U., & Linkermann, A. (2019) · The Journal of Pathology · doi:10.1002/path.5248 · Cited by 160 · see citing works
Self-citationThe Therapeutic and Pathogenic Role of Autophagy in Autoimmune Diseases
Yin, H., Wu, H., Chen, Y., Zhang, J., Zheng, M., Chen, G., Li, L., & Lu, Q. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01512 · Cited by 154 · see citing works
Self-citationAutophagy: controlling cell fate in rheumatic diseases
Rockel, J., & Kapoor, M. (2016) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2016.92 · Cited by 144 · see citing works
Microglial autophagy–associated phagocytosis is essential for recovery from neuroinflammation
Berglund, R., Guerreiro-Cacais, A. O., Adzemovic, M. Z., Zeitelhofer, M., Lund, H., Ewing, E., Ruhrmann, S., Nutma, E., Parsa, R., Thessen-Hedreul, M., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.abb5077 · Cited by 149 · see citing works
Role of autophagy in the pathogenesis of inflammatory bowel disease
Iida, T., Onodera, K., & Nakase, H. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i11.1944 · Cited by 146 · see citing works
Autophagy Regulates Stress Responses, Metabolism, and Anticancer Immunity
White, E., Lattime, E. C., & Guo, J. Y. (2021) · Trends in cancer · doi:10.1016/j.trecan.2021.05.003 · Cited by 136 · see citing works
Crashing the computer: apoptosis vs. necroptosis in neuroinflammation
Heckmann, B. L., Tummers, B., & Green, D. R. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0195-3 · Cited by 132 · see citing works
Self-citationProgrammed Cell Death and Inflammation: Winter Is Coming
Kolb, J. P., Oguin, T. H., Oberst, A., & Martinez, J. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.06.009 · Cited by 131 · see citing works
Self-citationSelective autophagy of the adaptor TRIF regulates innate inflammatory signaling
Samie, M., Lim, J., Verschueren, E., Baughman, J. M., Peng, I., Wong, A., Kwon, Y. C., Şenbabaoğlu, Y., Hackney, J. A., Keir, M. E., et al. (2018) · Nature Immunology · doi:10.1038/s41590-017-0042-6 · Cited by 130 · see citing works
Autophagy in Neutrophils: From Granulopoiesis to Neutrophil Extracellular Traps
Skendros, P., Mitroulis, I., & Ritis, K. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00109 · Cited by 129 · see citing works
Hu, X., Li, Z., Lin, R., Shan, J.-Q., Yu, Q., Wang, R., Liao, L., Yan, W., Zhen, W., Shang, L., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.634690 · Cited by 127 · see citing works
Yoshii, S. R., Kuma, A., Akashi, T., Hara, T., Yamamoto, A., Kurikawa, Y., Itakura, E., Tsukamoto, S., Shitara, H., Eishi, Y., et al. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.09.001 · Cited by 127 · see citing works
IRGM1 links mitochondrial quality control to autoimmunity
Rai, P., Janardhan, K. S., Meacham, J. M., Madenspacher, J. H., Lin, W.-C., Karmaus, P. W. F., Martinez, J., Li, Q., Yan, M., Zeng, J., et al. (2021) · Nature Immunology · doi:10.1038/s41590-020-00859-0 · Cited by 126 · see citing works
Self-citationMacrophage in chronic kidney disease
Guiteras, R., Flaquer, M., & Cruzado, J. M. (2016) · Clinical Kidney Journal · doi:10.1093/ckj/sfw096 · Cited by 123 · see citing works
Better Together: Current Insights Into Phagosome-Lysosome Fusion
Nguyen, J. A., & Yates, R. M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.636078 · Cited by 120 · see citing works
LAMP3 inhibits autophagy and contributes to cell death by lysosomal membrane permeabilization
Tanaka, T., Warner, B. M., Michael, D. G., Nakamura, H., Odani, T., Yin, H., Atsumi, T., Noguchi, M., & Chiorini, J. A. (2021) · Autophagy · doi:10.1080/15548627.2021.1995150 · Cited by 122 · see citing works
Recent Progress in Metal-Based Nanoparticles Mediated Photodynamic Therapy
Sun, J., Kormakov, S., Liu, Y., Huang, Y., Wu, D., & Yang, Z. (2018) · Molecules · doi:10.3390/molecules23071704 · Cited by 118 · see citing works
A water tunnel study of Gurney flaps
Neuhart, D., & Pendergraft, O. C. (1988) · NASA STI Repository (National Aeronautics and Space Administration) · Cited by 117 · see citing works
Qi, Y., Zhou, S., Cheng, F., Hou, P., Ren, Y., Wang, S., Zhao, M., Yang, L., Martinez, J., & Zhang, H. (2018) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2018-213028 · Cited by 116 · see citing works
Self-citationDeng, Y., & Tsao, B. P. (2017) · Current Rheumatology Reports · doi:10.1007/s11926-017-0695-z · Cited by 113 · 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
Self-citationCadwell, K., & Debnath, J. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201706157 · Cited by 106 · see citing works
Oh, D. S., & Lee, H. K. (2019) · Autophagy · doi:10.1080/15548627.2019.1596493 · Cited by 109 · see citing works
Macrophages target Salmonella by Lc3-associated phagocytosis in a systemic infection model
Masud, S., Prajsnar, T. K., Torraca, V., Lamers, G. E. M., Benning, M., van der Vaart, M., & Meijer, A. H. (2019) · Autophagy · doi:10.1080/15548627.2019.1569297 · Cited by 108 · see citing works
Autophagy dictates metabolism and differentiation of inflammatory immune cells
Riffelmacher, T., Richter, F. C., & Simon, A. K. (2017) · Autophagy · doi:10.1080/15548627.2017.1362525 · Cited by 107 · see citing works
FoxO3 activation in hypoxic tubules prevents chronic kidney disease
Li, L., Kang, H., Zhang, Q., D’Agati, V. D., Al-Awqati, Q., & Lin, F. (2019) · Journal of Clinical Investigation · doi:10.1172/jci122256 · Cited by 105 · see citing works
First we eat, then we do everything else: The dynamic metabolic regulation of efferocytosis
Trzeciak, A. J., Wang, Y., & Perry, J. S. A. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.08.001 · Cited by 107 · see citing works
Mitochondrial Dysfunction and Oxidative Stress in Rheumatoid Arthritis
López-Armada, M. J., Fernández-Rodríguez, J. A., & Blanco, F. J. (2022) · Antioxidants · doi:10.3390/antiox11061151 · Cited by 108 · see citing works
Podocytes and autophagy: a potential therapeutic target in lupus nephritis
Zhou, S., Klionsky, D. J., & Zhang, H. (2019) · Autophagy · doi:10.1080/15548627.2019.1580512 · Cited by 105 · see citing works
Lc3-associated phagocytosis—The highway to hell for phagocytosed microbes
Herb, M., Gluschko, A., & Schramm, M. (2020) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2019.04.016 · Cited by 103 · see citing works
Rai, S., Arasteh, J. M., Jefferson, M. A., Pearson, T., Wang, Y., Zhang, W., Bicsák, B., Divekar, D. P., Powell, P. P., Naumann, R., et al. (2018) · Autophagy · doi:10.1080/15548627.2018.1534507 · Cited by 98 · see citing works
Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation
Reglero-Real, N., Pérez, L., Yoshimura, A., Rolas, L., Garrido‐Mesa, J., Barkaway, A., Pickworth, C., Saleeb, R. S., Gonzalez-Nuñez, M., Austin‐Williams, S., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.07.012 · Cited by 103 · see citing works
Autophagy restricts Mycobacterium tuberculosis during acute infection in mice
Golovkine, G. R., Roberts, A. W., Morrison, H. M., Rivera‐Lugo, R., McCall, R. M., Nilsson, H., Garelis, N. E., Repasy, T., Cronce, M. J., Budzik, J. M., et al. (2023) · Nature Microbiology · doi:10.1038/s41564-023-01354-6 · Cited by 102 · see citing works
Rubicon: <scp>LC</scp>3‐associated phagocytosis and beyond
Wong, S., Sil, P., & Martinez, J. (2018) · The FEBS Journal · doi:10.1111/febs.14354 · Cited by 101 · see citing works
Self-citationHirose, S., Lin, Q., Ohtsuji, M., Nishimura, H., & Verbeek, J. S. (2019) · International Immunology · doi:10.1093/intimm/dxz036 · Cited by 101 · see citing works
Programmed Cell Death Pathways in the Pathogenesis of Systemic Lupus Erythematosus
Yang, F., He, Y., Zhai, Z., & Sun, E. (2019) · Journal of Immunology Research · doi:10.1155/2019/3638562 · Cited by 101 · see citing works
Kyrmizi, I., Ferreira, H., Carvalho, A., Figueroa, J. A. L., Zarmpas, P., Cunha, C., Akoumianaki, T., Stylianou, K., Deepe, G. S., Samonis, G., et al. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0167-x · Cited by 96 · see citing works
Immunological consequences of kidney cell death
Sarhan, M., von Mäßenhausen, A., Hugo, C., Oberbauer, R. W., & Linkermann, A. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0057-9 · Cited by 98 · see citing works
Self-citationHe, Y., Cao, X., Guo, P., Li, X., Shang, H., Liu, J., Xie, M., Xu, Y., & Liu, X. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.016 · Cited by 94 · see citing works
Lupus and proliferative nephritis are PAD4 independent in murine models
Gordon, R. A., Herter, J. M., Rosetti, F., Campbell, A. M., Nishi, H., Kashgarian, M. J., Bastacky, S., Marinov, A. D., Nickerson, K. M., Mayadas, T. N., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.92926 · Cited by 94 · see citing works
Unlocking the power of NOX2: A comprehensive review on its role in immune regulation
Bode, K., Hauri-Hohl, M. M., Jaquet, V., & Weyd, H. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102795 · Cited by 94 · see citing works
- Authors
- Martinez, J., Cunha, L. D., Park, S., Yang, M., Lu, Q., Orchard, R., Li, Q.-Z., Yan, M., Janke, L., Guy, C., Linkermann, A., Virgin, H. W., & Green, D. R.
- Affiliations
- National Institutes of Health (US)
- St. Jude Children's Research Hospital (US)
- Washington University in St. Louis (US)
- The University of Texas Southwestern Medical Center (US)
- Christian-Albrechts-Universität zu Kiel (DE)
- Corresponding author
- Martinez, Jennifer
- Green, Douglas R.
- ORCID
- Venue
- Nature
- Published
- 2016-04-20
- Volume
- 533
- Issue
- 7601
- Pages
- 115-119
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4860026
- OpenAlex
- W2338725336
- Cited by
- 381
- References
- 31
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 17 · 2023: 21 · 2022: 52 · 2021: 57 · 2020: 41 · 2019: 52 · 2018: 50 · 2017: 52 · 2016: 31
- FWCI
- 65.62
- Type
- journal article
- Language
- en
- Status
- Retracted
- Update notices
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (1ZIAES10328601)
- National Cancer Institute (P30CA021765)
- National Institute of Allergy and Infectious Diseases (R01AI040646, R01AI40646, U19AI109725, T32AI007163)
- National Institute of Environmental Health Sciences (ZIAES103286)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- LC3-associated phagocytosis, non-canonical autophagy, systemic lupus erythematosus, autoinflammation, autoantibodies, anti-DNA antibodies, phagosome maturation, ATG5, ATG7, kidney disease, inflammatory cytokines, autoimmunity, retracted article
- MeSH terms
- Animals, Antigen-Antibody Complex, Autoantibodies, Autophagy, Inflammation, Kidney, Lupus Erythematosus, Systemic, Male, Microtubule-Associated Proteins, Phagocytes, Phagosomes, Cytokines, Interleukin-10, Mice
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