Age-related increases in PGD2 expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice
Open accessAbstract
The morbidity and mortality associated with respiratory virus infection is felt most keenly among the elderly. T cells are necessary for viral clearance, and many age-dependent intrinsic T cell defects have been documented. However, the development of robust T cell responses in the lung also requires respiratory DCs (rDCs), which must process antigen and migrate to draining LNs (DLNs), and little is known about age-related defects in these T cell-extrinsic functions. Here, we show that increases in prostaglandin D(2) (PGD(2)) expression in mouse lungs upon aging correlate with a progressive impairment in rDC migration to DLNs. Decreased rDC migration resulted in diminished T cell responses and more severe clinical disease in older mice infected with respiratory viruses. Diminished rDC migration associated with virus-specific defects in T cell responses and was not a result of cell-intrinsic defect, rather it reflected the observed age-dependent increases in PGD(2) expression. Blocking PGD(2) function with small-molecule antagonists enhanced rDC migration, T cell responses, and survival. This effect correlated with upregulation on rDCs of CCR7, a chemokine receptor involved in DC chemotaxis. Our results suggest that inhibiting PGD(2) function may be a useful approach to enhance T cell responses against respiratory viruses in older humans.
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
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?
Age-related elevations of eicosanoid levels, especially prostaglandin D2 (PGD2), were detected in mouse models of SARS-CoV infection.
“Age-related elevations of eicosanoid levels, especially prostaglandin D2 (PGD2), were detected in mouse models of SARS-CoV infection133.”
From COVID-19 and cellular senescence (2023) · cites this paper as [133]
During SARS-CoV-1 infection, lung dendritic cells from older mice had impaired migration to the draining lymph node, which negatively affected subsequent T cell priming.
“During SARS-CoV-1 infection, lung DCs from older mice displayed an impaired ability to migrate to the draining lymph node, which negatively affected subsequent T cell priming125.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [125]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mortality Associated With Influenza and Respiratory Syncytial Virus in the United States
Thompson, W. W., Shay, D. K., Weintraub, E., Brammer, L., Cox, N., Anderson, L. J., & Fukuda, K. (2003) · JAMA · doi:10.1001/jama.289.2.179 · Cited by 3,673 · see citing works
Severe acute respiratory syndrome
Peiris, M. J. S., Guan, Y., & Yuen, K. (2004) · Nature Medicine · doi:10.1038/nm1143 · Cited by 1,135 · see citing works
Human Host Factors Required for Influenza Virus Replication
König, R., Stertz, S., Zhou, Y.-Y., Inoue, A., Hoffmann, H., Bhattacharyya, S., Alamares, J. G., Tscherne, D. M., Ortigoza, M., Liang, Y.-H., et al. (2010) · Nature · doi:10.1038/nature08699 · Cited by 866 · see citing works
Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication
Karlas, A., Machuy, N., Shin, Y.-J., Pleissner, K., Artarini, A., Heuer, D., Becker, D., Khalil, H., Ogilvie, L., Hess, S., et al. (2010) · Nature · doi:10.1038/nature08760 · Cited by 715 · see citing works
A Physical and Regulatory Map of Host-Influenza Interactions Reveals Pathways in H1N1 Infection
Shapira, S. D., Gat‐Viks, I., Shum, B. O. V., Dricot, A., DeGrace, M. M., Wu, L., Gupta, P. B., Hao, T., Silver, S. J., Root, D. E., et al. (2009) · Cell · doi:10.1016/j.cell.2009.12.018 · Cited by 630 · see citing works
RNA interference screen for human genes associated with West Nile virus infection
Krishnan, M. N., Ng, A., Sukumaran, B., Gilfoy, F. D., Uchil, P., Sultana, H., Brass, A., Adametz, R., Tsui, M., Qian, F., et al. (2008) · Nature · doi:10.1038/nature07207 · Cited by 542 · see citing works
Vermaelen, K. Y., Carro‐Muino, I., Lambrecht, B. N., & PAUWELS, R. A. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.193.1.51 · Cited by 542 · see citing works
Yager, E. J., Ahmed, M., Lanzer, K., Randall, T. D., Woodland, D. L., & Blackman, M. A. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20071140 · Cited by 490 · see citing works
Sung, S. J., Fu, S. M., Rose, C. E., Gaskin, F., Ju, S., & Beaty, S. R. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.4.2161 · Cited by 476 · see citing works
Migration of Dendritic Cell Subsets and their Precursors
Randolph, G. J., Ochando, J., & Partida‐Sánchez, S. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090254 · Cited by 468 · see citing works
Bouchon, A., Hernández-Munain, C., Cella, M., & Colonna, M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.8.1111 · Cited by 460 · see citing works
A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice
Roberts, A., Deming, D., Paddock, C. D., Cheng, A., Yount, B. L., Vogel, L., Herman, B. D., Sheahan, T., Heise, M. T., Genrich, G. L., et al. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030005 · Cited by 447 · see citing works
Cutting Edge: Rapid In Vivo Killing by Memory CD8 T Cells
Barber, D. L., Wherry, E. J., & Ahmed, R. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.1.27 · Cited by 444 · see citing works
McWilliam, A. S., Nelson, D. J., Thomas, J. A., & Holt, P. G. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.4.1331 · Cited by 382 · see citing works
Legge, K. L., & Braciale, T. J. (2003) · Immunity · doi:10.1016/s1074-7613(03)00023-2 · Cited by 353 · see citing works
Self-citationPlackett, T. P., Boehmer, E. D., Faunce, D. E., & Kovacs, E. J. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.1103592 · Cited by 351 · see citing works
Antagonism of the prostaglandin D2 receptors DP1 and CRTH2 as an approach to treat allergic diseases
Pettipher, R., Hansel, T. T., & Armer, R. E. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2266 · Cited by 320 · see citing works
del Rio, M., Rodríguez-Barbosa, J.-I., Kremmer, E., & Förster, R. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.11.6861 · Cited by 319 · see citing works
The lung as a privileged site for the beneficial actions of PGE2
Vancheri, C. (2003) · Trends in Immunology · doi:10.1016/j.it.2003.11.001 · Cited by 313 · see citing works
Nagata, K., Hirai, H., Tanaka, K., Ogawa, K., Asô, T., Sugamura, K., Nakamura, M., & Takano, S. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01251-x · Cited by 297 · see citing works
Kim, T. S., & Braciale, T. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004204 · Cited by 279 · see citing works
Comparative Efficacy of Inactivated and Live Attenuated Influenza Vaccines
Monto, A. S., Ohmit, S. E., Petrie, J. G., Johnson, E., Truscon, R., Teich, E., Rotthoff, J. R., Boulton, M. L., & Victor, J. C. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808652 · Cited by 277 · see citing works
The Multiple Personalities of the Chemokine Receptor CCR7 in Dendritic Cells
Sánchez‐Sánchez, N., Riol‐Blanco, L., & Rodríguez‐Fernández, J. L. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.9.5153 · Cited by 274 · see citing works
Angéli, V., Faveeuw, C., Roye, O., Fontaine, J., Teissier, E., Capron, A., Wolowczuk, I., Capron, M., & Trottein, F. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.10.1135 · Cited by 274 · see citing works
Ballesteros‐Tato, A., León, B., Lund, F. E., & Randall, T. D. (2010) · Nature Immunology · doi:10.1038/ni.1838 · Cited by 268 · see citing works
The Anti-Inflammatory Effects of Prostaglandins
Scher, J. U., & Pillinger, M. H. (2009) · Journal of Investigative Medicine · doi:10.2310/jim.0b013e31819aaa76 · Cited by 259 · see citing works
Impaired immune responses in the lungs of aged mice following influenza infection
Toapanta, F. R., & Ross, T. M. (2009) · Respiratory Research · doi:10.1186/1465-9921-10-112 · Cited by 259 · see citing works
Hervé, M., Angéli, V., Pinzar, E., Wintjens, R. T., Faveeuw, C., Narumiya, S., Capron, A., Urade, Y., Capron, M., Riveau, G. J., et al. (2003) · European Journal of Immunology · doi:10.1002/eji.200324143 · Cited by 256 · see citing works
Modulation of Dendritic Cell Trafficking to and from the Airways
Jakubzick, C., Tacke, F., Llodrá, J., van Rooijen, N., & Randolph, G. J. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.6.3578 · Cited by 251 · see citing works
Crowe, S. R., Turner, S. J., Miller, S. C., Roberts, A. D., Rappolo, R. A., Doherty, P. C., Ely, K. H., & Woodland, D. L. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20022151 · Cited by 218 · see citing works
Hammad, H., de Heer, H. J., Soullié, T., Hoogsteden, H. C., Trottein, F., & Lambrecht, B. N. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.8.3936 · Cited by 194 · see citing works
Giles, H., Leff, P., Bolofo, M. L., Kelly, M. G., & Robertson, A. D. (1989) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1989.tb11816.x · Cited by 192 · see citing works
Beaty, S. R., Rose, C. E., & Sung, S. J. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.3.1882 · Cited by 183 · see citing works
Rockx, B., Baas, T., Zornetzer, G. A., Haagmans, B. L., Sheahan, T. P., Frieman, M. B., Dyer, M. D., Teal, T. H., Proll, S. C., van den Brand, J. M. A., et al. (2009) · Journal of Virology · doi:10.1128/jvi.00127-09 · Cited by 175 · see citing works
Aging and innate immunity in the mouse: impact of intrinsic and extrinsic factors
Kovacs, E., Palmer, J. L., Fortin, C., Fülöp, T., Goldstein, D., & Linton, P. (2009) · Trends in immunology · doi:10.1016/j.it.2009.03.012 · Cited by 173 · see citing works
Sturino, C. F., O’Neill, G. P., Lachance, N., Boyd, M. J., Berthelette, C., Labelle, M., Li, L., Roy, B., Scheigetz, J., Tsou, N. N., et al. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm0603668 · Cited by 171 · see citing works
Albuquerque, N. D., Baig, E., Ma, X., Zhang, J., He, W. R., Rowe, A., Habal, M. V., Liu, M., Shalev, I., Downey, G. P., et al. (2006) · Journal of Virology · doi:10.1128/jvi.00747-06 · Cited by 167 · see citing works
Paolini, J. F., Mitchel, Y., Reyes, R., Kher, U. A., Lai, E., Watson, D. J., Norquist, J. M., Meehan, A. G., Bays, H. E., Davidson, M., et al. (2007) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2007.10.023 · Cited by 163 · see citing works
Trandem, K., Zhao, J., Fleming, E., & Perlman, S. M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003292 · Cited by 158 · see citing works
Self-citationKey role of T cell defects in age-related vulnerability to West Nile virus
Brien, J. D., Uhrlaub, J. L., Hirsch, A., Wiley, C. A., & Nikolich-Žugich, J. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20090222 · Cited by 158 · see citing works
Omega-3 Fatty Acids and Inflammation: Novel Interactions Reveal a New Step in Neutrophil Recruitment
Tull, S. P., Yates, C. M., Maskrey, B. H., O’Donnell, V. B., Madden, J., Grimble, R. F., Calder, P. C., Nash, G. B., & Rainger, G. E. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000177 · Cited by 154 · see citing works
Zhao, J., Zhao, J., van Rooijen, N., & Perlman, S. M. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000636 · Cited by 151 · see citing works
Self-citationLymph Node Dendritic Cells Control CD8+ T Cell Responses through Regulated FasL Expression
Legge, K. L., & Braciale, T. J. (2005) · Immunity · doi:10.1016/j.immuni.2005.11.006 · Cited by 140 · see citing works
Self-citationIntrinsic versus environmental influences on T‐cell responses in aging
Linton, P., Li, S. P., Zhang, Y., Bautista, B., Huynh, Q. L., & Trinh, T. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00266.x · Cited by 115 · see citing works
Biology of Dendritic Cells in Aging
Agrawal, A., Agrawal, S., Tay, J., & Gupta, S. (2007) · Journal of Clinical Immunology · doi:10.1007/s10875-007-9127-6 · Cited by 112 · see citing works
Meyer, K. C. (2010) · Seminars in Respiratory and Critical Care Medicine · doi:10.1055/s-0030-1265897 · Cited by 94 · see citing works
Response of aged mice to primary virus infections
Murasko, D. M., & Jiang, J. K. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00273.x · Cited by 93 · see citing works
Katz, J. M., Plowden, J., Renshaw‐Hoelscher, M., Lu, X., Tumpey, T. M., & Sambhara, S. R. (2004) · Immunologic Research · doi:10.1385/ir:29:1-3:113 · Cited by 88 · see citing works
Prostanoids and inflammation: a new concept arising from receptor knockout mice
Narumiya, S. (2009) · Journal of Molecular Medicine · doi:10.1007/s00109-009-0500-1 · Cited by 86 · see citing works
Nagata, N., Iwata, N., Hasegawa, H., Fukushi, S., Harashima, A., Sato, Y., Saijo, M., Taguchi, F., Morikawa, S., & Sata, T. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.071060 · Cited by 82 · see citing works
Aging and the dendritic cell system: Implications for cancer
Shurin, M. R., Shurin, G. V., & Chatta, G. S. (2007) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2007.03.002 · Cited by 76 · see citing works
Regulation of Immune Cells by Eicosanoid Receptors
Kim, N. D., & Luster, A. D. (2007) · The Scientific World JOURNAL · doi:10.1100/tsw.2007.181 · Cited by 69 · see citing works
Contrary prostaglandins: the opposing roles of PGD2 and its metabolites in leukocyte function
Sandig, H., Pease, J. E., & Sabroe, I. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.0706424 · Cited by 64 · see citing works
Gosset, P., Pichavant, M., Faveeuw, C., Bureau, F., Tonnel, A., & Trottein, F. (2005) · European Journal of Immunology · doi:10.1002/eji.200425319 · Cited by 63 · see citing works
Mechanotransduction of stretch-induced prostanoid release by fetal lung epithelial cells
Copland, I. B., Reynaud, D., Pace-Asciak, C. R., & Post, M. (2006) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00510.2005 · Cited by 55 · see citing works
Zhou, H., Zhao, J., & Perlman, S. M. (2010) · mBio · doi:10.1128/mbio.00219-10 · Cited by 45 · see citing works
Self-citationAging and CD8+ T cell immunity to respiratory virus infections
ELY, K., ROBERTS, A., Kohlmeier, J. E., Blackman, M. A., & Woodland, D. L. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2006.11.017 · Cited by 44 · see citing works
Höpken, U. E., & Lipp, M. (2004) · Immunity · doi:10.1016/s1074-7613(04)00056-1 · Cited by 36 · see citing works
dos Santos, S. S., Ferreira, K. S., & de Almeida, S. R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019690 · Cited by 34 · see citing works
Sanyal, S., Kuvin, J. T., & Karas, R. H. (2010) · Drugs of today · doi:10.1358/dot.2010.46.6.1464844 · Cited by 20 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Paolini JF, et al. Effects of laropiprant on nicotinic acid-induced flushing in patients with dyslipid- emia. Am J Cardiol. 2008;101(5):625-630.
- Sanyal S, Kuvin JT, Karas RH. Niacin and laropip- rant. Drugs Today (Barc). 2010;46(6):371-378.
Cited by
Sorted by citations
The trinity of COVID-19: immunity, inflammation and intervention
Tay, M. Z., Poh, C. M., Rénia, L., MacAry, P. A., & Ng, L. F. P. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0311-8 · Cited by 4,360 · see citing works
Coronaviruses: An Overview of Their Replication and Pathogenesis
Fehr, A. R., & Perlman, S. M. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2438-7_1 · Cited by 3,784 · see citing works
Self-citationGrifoni, A., Weiskopf, D., Ramirez, S. I., Mateus, J., Dan, J. M., Moderbacher, C. R., Rawlings, S. A., Sutherland, A., Premkumar, L., Jadi, R. S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.015 · Cited by 3,595 · see citing works
Channappanavar, R., & Perlman, S. (2017) · Seminars in Immunopathology · doi:10.1007/s00281-017-0629-x · Cited by 2,524 · see citing works
Self-citationRydyznski Moderbacher, C., Ramirez, S. I., Dan, J. M., Grifoni, A., Hastie, K. M., Weiskopf, D., Belanger, S., Abbott, R. K., Kim, C., Choi, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.038 · Cited by 1,790 · see citing works
“…immune evasion by SARS-CoV-2 may limit T cell priming (Blanco-Melo et al., 2020; Vabret et al., 2020), and there is the possibility of fewer professional antigen presenting cells in the lungs with advanced age, as has been seen in small animal models of SARS (Chen et al., 2010; Zhao et al., 2011).”
Liu, J., Li, S., Liu, J., Liang, B., Wang, X., Wang, H., Li, W., Tong, Q., Yi, J., Zhao, L., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102763 · Cited by 1,702 · see citing works
Channappanavar, R., Fehr, A. R., Vijay, R., Mack, M., Zhao, J., Meyerholz, D. K., & Perlman, S. M. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.01.007 · Cited by 1,400 · see citing works
Self-citationThe twilight of immunity: emerging concepts in aging of the immune system
Nikolich-Žugich, J. (2018) · Nature Immunology · doi:10.1038/s41590-017-0006-x · Cited by 1,240 · see citing works
Coperchini, F., Chiovato, L., Croce, L., Magri, F., & Rotondi, M. (2020) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2020.05.003 · Cited by 1,288 · see citing works
From SARS to MERS, Thrusting Coronaviruses into the Spotlight
Song, Z., Xu, Y., Bao, L., Zhang, L., Yü, P., Qu, Y., Zhu, H., Zhao, W., Han, Y., & Qin, C. (2019) · Viruses · doi:10.3390/v11010059 · Cited by 1,268 · see citing works
Age-dependent dysregulation of innate immunity
Shaw, A. C., Goldstein, D. R., & Montgomery, R. R. (2013) · Nature Reviews Immunology · doi:10.1038/nri3547 · Cited by 1,061 · see citing works
Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection
Channappanavar, R., Fett, C., Mack, M., Eyck, P. T., Meyerholz, D. K., & Perlman, S. M. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601896 · Cited by 896 · see citing works
Self-citationDendritic cell migration in health and disease
Worbs, T., Hammerschmidt, S. I., & Förster, R. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.116 · Cited by 826 · see citing works
COVID-19 and the human innate immune system
Schultze, J. L., & Aschenbrenner, A. C. (2021) · Cell · doi:10.1016/j.cell.2021.02.029 · Cited by 714 · see citing works
A decade after SARS: strategies for controlling emerging coronaviruses
Graham, R. L., Donaldson, E., & Baric, R. S. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro3143 · Cited by 676 · see citing works
IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes
Channappanavar, R., Fehr, A. R., Zheng, J. H., Wohlford-Lenane, C., Abrahante, J. E., Mack, M., Sompallae, R. R., McCray, P. B., Meyerholz, D. K., & Perlman, S. M. (2019) · Journal of Clinical Investigation · doi:10.1172/jci126363 · Cited by 556 · see citing works
Self-citationT cell-mediated immune response to respiratory coronaviruses
Channappanavar, R., Zhao, J., & Perlman, S. (2014) · Immunologic Research · doi:10.1007/s12026-014-8534-z · Cited by 512 · see citing works
Self-citationAirway Memory CD4+ T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses
Zhao, J., Zhao, J., Mangalam, A. K., Channappanavar, R., Fett, C., Meyerholz, D. K., Agnihothram, S., Baric, R. S., David, C. S., & Perlman, S. (2016) · Immunity · doi:10.1016/j.immuni.2016.05.006 · Cited by 496 · see citing works
Self-citationThe aging lung: Physiology, disease, and immunity
Schneider, J. L., Rowe, J. H., Garcia-de-Alba, C., Kim, C. F., Sharpe, A. H., & Haigis, M. C. (2021) · Cell · doi:10.1016/j.cell.2021.03.005 · Cited by 500 · see citing works
Rapid generation of a mouse model for Middle East respiratory syndrome
Zhao, J., Li, K., Wohlford-Lenane, C., Agnihothram, S., Fett, C., Zhao, J., Gale, M., Baric, R. S., Enjuanes, L., Gallagher, T., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323279111 · Cited by 453 · see citing works
Self-citationChannappanavar, R., Fett, C., Zhao, J., Meyerholz, D. K., & Perlman, S. (2014) · Journal of Virology · doi:10.1128/jvi.01505-14 · Cited by 411 · see citing works
Self-citationSARS-CoV-2, COVID-19 and the aging immune system
Bartleson, J. M., Radenkovic, D., Covarrubias, A. J., Furman, D., Winer, D. A., & Verdin, E. (2021) · Nature Aging · doi:10.1038/s43587-021-00114-7 · Cited by 359 · see citing works
Liang, Y., Wang, M., Chien, C., Yarmishyn, A. A., Yang, Y.-P., Lai, W.-Y., Luo, Y., Lin, Y.-T., Chen, Y.-J., Chang, P., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01022 · Cited by 339 · see citing works
Early local immune defences in the respiratory tract
Iwasaki, A., Foxman, E. F., & Molony, R. D. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.117 · Cited by 331 · see citing works
Lessons for COVID-19 immunity from other coronavirus infections
Sariol, A., & Perlman, S. (2020) · Immunity · doi:10.1016/j.immuni.2020.07.005 · Cited by 317 · see citing works
Self-citationMechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury
Gralinski, L. E., Bankhead, A., Jeng, S., Menachery, V. D., Proll, S. C., Belisle, S. E., Matzke, M. M., Webb‐Robertson, B., Luna, M. L., Shukla, A. K., et al. (2013) · mBio · doi:10.1128/mbio.00271-13 · Cited by 310 · see citing works
Pharmaco-Immunomodulatory Therapy in COVID-19
Rizk, J. G., Kalantar‐Zadeh, K., Mehra, M. R., Lavie, C. J., Rizk, Y., & Forthal, D. N. (2020) · Drugs · doi:10.1007/s40265-020-01367-z · Cited by 289 · see citing works
Immune Senescence, Immunosenescence and Aging
Lee, K.-A., Flores, R. R., Jang, I. H., Saathoff, A., & Robbins, P. D. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.900028 · Cited by 283 · see citing works
The Confluence of Sex Hormones and Aging on Immunity
Gubbels Bupp, M. R., Potluri, T., Fink, A. L., & Klein, S. L. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01269 · Cited by 277 · see citing works
Aging, inflammation, immunity and periodontal disease
Ebersole, J. L., Graves, C. L., González, O. A., Dawson, D. R., Morford, L. A., Emecen‐Huja, P., Hartsfield, J. K., Huja, S. S., Pandruvada, S. N. M., & Wallet, S. M. (2016) · Periodontology 2000 · doi:10.1111/prd.12135 · Cited by 308 · see citing works
Kovacs, E. J., Lowery, E. M., Kuhlmann, E. A., & Brubaker, A. L. (2013) · Clinical Interventions in Aging · doi:10.2147/cia.s51152 · Cited by 280 · see citing works
Recovery from the Middle East respiratory syndrome is associated with antibody and T cell responses
Zhao, J., Alshukairi, A. N., Baharoon, S. A., Ahmed, W., Bokhari, A. A., Nehdi, A., Layqah, L. A., Alghamdi, M., Algethamy, M., Dada, A. M., et al. (2017) · Science Immunology · doi:10.1126/sciimmunol.aan5393 · Cited by 259 · see citing works
Self-citationAging Impairs Alveolar Macrophage Phagocytosis and Increases Influenza-Induced Mortality in Mice
Wong, C. K., Smith, C. A., Sakamoto, K., Kaminski, N., Koff, J. L., & Goldstein, D. R. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700397 · Cited by 246 · see citing works
Islam, M. T., Sarkar, C. K., El‐Kersh, D. M., Jamaddar, S., Uddin, S. J., Shilpi, J. A., & Mubarak, M. S. (2020) · Phytotherapy Research · doi:10.1002/ptr.6700 · Cited by 230 · see citing works
Coronaviruses: An Updated Overview of Their Replication and Pathogenesis
Wang, Y., Grunewald, M. E., & Perlman, S. M. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0900-2_1 · Cited by 207 · see citing works
Self-citationZhu, H., Rhee, J., Cheng, P. P., Waliany, S., Chang, A., Witteles, R. M., Maecker, H. T., Davis, M. M., Nguyen, P. K. P., & Wu, S. M. (2020) · Current Cardiology Reports · doi:10.1007/s11886-020-01292-3 · Cited by 211 · see citing works
The Immune Response and Immunopathology of COVID-19
Mortaz, E., Tabarsi, P., Varahram, M., Folkerts, G., & Adcock, I. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02037 · Cited by 206 · see citing works
Wong, L.-Y. R., & Perlman, S. M. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00656-2 · Cited by 196 · see citing works
Self-citationEicosanoid signalling blockade protects middle-aged mice from severe COVID-19
Wong, L.-Y. R., Zheng, J., Wilhelmsen, K., Li, K., Ortiz, M. E., Schnicker, N. J., Thurman, A., Pezzulo, A. A., Szachowicz, P. J., Li, P., et al. (2022) · Nature · doi:10.1038/s41586-022-04630-3 · Cited by 178 · see citing works
Self-citationMapping and role of T cell response in SARS-CoV-2–infected mice
Zhuang, Z., Lai, X., Sun, J., Chen, Z., Zhang, Z., Dai, J., Liu, D., Li, Y., Li, F., Wang, Y., et al. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20202187 · Cited by 171 · see citing works
Self-citationHigh levels of eicosanoids and docosanoids in the lungs of intubated COVID‐19 patients
Archambault, A., Zaid, Y., Rakotoarivelo, V., Turcotte, C., Doré, É., Dubuc, I., Martin, C., Flamand, O., Amar, Y., Cheikh, A., et al. (2021) · The FASEB Journal · doi:10.1096/fj.202100540r · Cited by 173 · see citing works
Emerging SARS-CoV-2 variants expand species tropism to murines
Shuai, H., Chan, J. F., Yuen, T. T., Yoon, C., Hu, J., Wen, L., Hu, B., Yang, D., Wang, Y., Hou, Y., et al. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103643 · Cited by 171 · see citing works
Sokołowska, M., Łukasik, Z. M., Agache, I. O., Akdiş, C. A., Akdiş, D., Akdiş, M., Barcik, W., Brough, H. A., Eiwegger, T., Eljaszewicz, A., et al. (2020) · Allergy · doi:10.1111/all.14462 · Cited by 169 · see citing works
Blue Journal Conference. Aging and Susceptibility to Lung Disease
Thannickal, V. J., Murthy, M., Balch, W. E., Chandel, N. S., Meiners, S., Eickelberg, O., Selman, M., Pardo, A., White, E. S., Levy, B. D., et al. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201410-1876pp · Cited by 164 · see citing works
Innate immune responses in the ageing lung.
Boe, D. M., Boule, L. A., & Kovacs, E. J. (2016) · Clinical and Experimental Immunology · doi:10.1111/cei.12881 · Cited by 156 · see citing works
Sims, A. M., Tilton, S. C., Menachery, V. D., Gralinski, L. E., Schäfer, A., Matzke, M. M., Webb‐Robertson, B., Chang, J., Luna, M. L., Long, C., et al. (2013) · Journal of Virology · doi:10.1128/jvi.02520-12 · Cited by 156 · see citing works
Immune responses during COVID-19 infection
Melenotte, C., Silvin, A., Goubet, A., Lahmar, I., Dubuisson, A., Zumla, A. I., Raoult, D., Merad-Boudia, M., Gachot, B., Henon, C., et al. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1807836 · Cited by 162 · see citing works
Brandenberger, C., & Mühlfeld, C. (2017) · Cell and Tissue Research · doi:10.1007/s00441-016-2511-x · Cited by 152 · see citing works
COVID-19 and cellular senescence
Schmitt, C. A., Tchkonia, T., Niedernhofer, L. J., Robbins, P. D., Kirkland, J. L., & Lee, S. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-022-00785-2 · Cited by 153 · see citing works
Chen, J., Alfajaro, M. M., Chow, R. D.-W., Wei, J., Filler, R. B., Eisenbarth, S. C., & Wilen, C. B. (2021) · Journal of Virology · doi:10.1128/jvi.00014-21 · Cited by 153 · see citing works
Dysbiosis, malnutrition and enhanced gut-lung axis contribute to age-related respiratory diseases
Saint‐Criq, V., Lugo‐Villarino, G., & Thomas, M. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101235 · Cited by 143 · see citing works
Intranasal Treatment with Poly(I·C) Protects Aged Mice from Lethal Respiratory Virus Infections
Zhao, J., Wohlford-Lenane, C., Zhao, J., Fleming, E., Lane, T. E., McCray, P. B., & Perlman, S. M. (2012) · Journal of Virology · doi:10.1128/jvi.01410-12 · Cited by 140 · see citing works
Self-citationVijay, R., Hua, X., Meyerholz, D. K., Miki, Y., Yamamoto, K., Gelb, M. H., Murakami, M., & Perlman, S. M. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20150632 · Cited by 139 · see citing works
Self-citationThe immuno-oncological challenge of COVID-19
Derosa, L., Melenotte, C., Griscelli, F., Gachot, B., Marabelle, A., Kroemer, G., & Zitvogel, L. (2020) · Nature Cancer · doi:10.1038/s43018-020-00122-3 · Cited by 133 · see citing works
Impact of aging on antigen presentation cell function of dendritic cells
Wong, C. K., & Goldstein, D. R. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.05.016 · Cited by 129 · see citing works
Reizine, F., Lesouhaitier, M., Grégoire, M., Pinceaux, K., Gacouin, A., Maamar, A., Painvin, B., Camus, C., Tulzo, Y. L., Tattevin, P., et al. (2021) · Journal of Clinical Immunology · doi:10.1007/s10875-020-00920-5 · Cited by 121 · see citing works
Fett, C., DeDiego, M. L., Regla-Nava, J. Á., Enjuanes, L., & Perlman, S. M. (2013) · Journal of Virology · doi:10.1128/jvi.00087-13 · Cited by 118 · see citing works
Self-citationPGD Synthase and PGD 2 in Immune Resposne
Joo, M., & Sadikot, R. T. (2012) · Mediators of Inflammation · doi:10.1155/2012/503128 · Cited by 110 · see citing works
Dual Nature of Type I Interferons in SARS-CoV-2-Induced Inflammation
King, C., & Sprent, J. (2021) · Trends in Immunology · doi:10.1016/j.it.2021.02.003 · Cited by 101 · see citing works
Innate immunesenescence: underlying mechanisms and clinical relevance
Hazeldine, J., & Lord, J. M. (2015) · Biogerontology · doi:10.1007/s10522-014-9514-3 · Cited by 104 · see citing works
Agnihothram, S., Gopal, R., Yount, B. L., Donaldson, E., Menachery, V. D., Graham, R. L., Scobey, T., Gralinski, L. E., Denison, M. R., Zambon, M. C. F. A., et al. (2013) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit609 · Cited by 104 · see citing works
Immunosenescence and Novel Vaccination Strategies for the Elderly
Dorrington, M. G., & Bowdish, D. M. E. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00171 · Cited by 104 · see citing works
Non‐steroidal anti‐inflammatory drugs, prostaglandins, and COVID‐19
Robb, C. T., Goepp, M., Rossi, A. G., & Yao, C. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15206 · Cited by 103 · see citing works
Cellular senescence as a potential mediator of COVID‐19 severity in the elderly
Nehme, J., Borghesan, M., Mackedenski, S., Bird, T. G., & Demaria, M. (2020) · Aging Cell · doi:10.1111/acel.13237 · Cited by 94 · see citing works
Zhang, Y.-Y., Li, B.-R., & Ning, B. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02033 · Cited by 103 · see citing works
The untwining of immunosenescence and aging
Xu, W., Wong, G. C. L., Hwang, Y. Y., & Larbi, A. (2020) · Seminars in Immunopathology · doi:10.1007/s00281-020-00824-x · Cited by 104 · see citing works
COVID-19 preclinical models: human angiotensin-converting enzyme 2 transgenic mice
Lutz, C. M., Maher, L. A., Lee, C., & Kang, W. (2020) · Human Genomics · doi:10.1186/s40246-020-00272-6 · Cited by 92 · see citing works
Channappanavar, R., & Perlman, S. M. (2020) · Journal of Clinical Investigation · doi:10.1172/jci144115 · Cited by 92 · see citing works
Self-citationBrandão, S. C. S., Ramos, J. D. O. X., Dompieri, L. T., Godoi, E. T. A. M., de Figueiredo, J. L., SARINHO, E. S. C., Chelvanambi, S., & Aikawa, M. (2020) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2020.09.002 · Cited by 93 · see citing works
The roles of lipids in SARS-CoV-2 viral replication and the host immune response
Theken, K. N., Tang, S. Y., Sengupta, S., & FitzGerald, G. A. (2021) · Journal of Lipid Research · doi:10.1016/j.jlr.2021.100129 · Cited by 89 · see citing works
COVID-19: Inflammatory Profile
Wang, Y., & Perlman, S. M. (2021) · Annual Review of Medicine · doi:10.1146/annurev-med-042220-012417 · Cited by 89 · see citing works
Self-citationThe role of lung dendritic cell subsets in immunity to respiratory viruses
Neyt, K., & Lambrecht, B. N. (2013) · Immunological Reviews · doi:10.1111/imr.12100 · Cited by 88 · see citing works
Linton, P., & Thoman, M. L. (2014) · Immunology Letters · doi:10.1016/j.imlet.2014.06.017 · Cited by 86 · see citing works
Immunosenescence and vaccine failure in the elderly: strategies for improving response
Boraschi, D., & Italiani, P. (2014) · Immunology Letters · doi:10.1016/j.imlet.2014.06.006 · Cited by 86 · see citing works
The role of dysregulated immune responses in COVID-19 pathogenesis
Tahaghoghi-Hajghorbani, S., Zafari, P., Masoumi, E., Rajabinejad, M., Jafari-Shakib, R., Hasani, B., & Rafiei, A. (2020) · Virus Research · doi:10.1016/j.virusres.2020.198197 · Cited by 87 · see citing works
Age and Periodontal Health—Immunological View
Ebersole, J. L., Dawson, D. R., Emecen‐Huja, P., Pandruvada, S. N. M., Basu, A., Nguyen, L., Zhang, Y., & González, O. A. (2018) · Current Oral Health Reports · doi:10.1007/s40496-018-0202-2 · Cited by 84 · see citing works
Immunomodulatory Effects of Azithromycin Revisited: Potential Applications to COVID-19
Venditto, V. J., Haydar, D., Abdel‐Latif, A., Gensel, J. C., Anstead, M., Pitts, M. G., Creameans, J. W., Kopper, T. J., Peng, C., & Feola, D. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.574425 · Cited by 86 · see citing works
Yasui, F., Kohara, M., Kitabatake, M., Nishiwaki, T., Fujii, H., Tateno, C., Yoneda, M., Morita, K., Matsushima, K., Koyasu, S., et al. (2014) · Virology · doi:10.1016/j.virol.2014.02.005 · Cited by 83 · see citing works
Chen, J., Kelley, W. J., & Goldstein, D. R. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.2000380 · Cited by 80 · see citing works
Home as the new frontier for the treatment of COVID-19: the case for anti-inflammatory agents
Perico, N., Cortinovis, M., Suter, F., & Remuzzi, G. (2022) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(22)00433-9 · Cited by 80 · see citing works
Caballero‐Solares, A., Hall, J. R., Xue, X., Eslamloo, K., Taylor, R. G., Parrish, C. C., & Rise, M. L. (2017) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2017.02.040 · Cited by 79 · see citing works
Gralinski, L. E., Menachery, V. D., Morgan, A. P., Totura, A. L., Beall, A. E., Kocher, J., Plante, J. A., Harrison-Shostak, D. C., Schäfer, A., de Villena, F. P., et al. (2017) · G3 Genes Genomes Genetics · doi:10.1534/g3.117.041434 · Cited by 75 · see citing works
Polyunsaturated Fatty Acid-Derived Lipid Mediators and T Cell Function
Nicolaou, A., Mauro, C., Urquhart, P., & Marelli‐Berg, F. M. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00075 · Cited by 75 · see citing works
The Contribution of Oxidative Stress and Inflamm-Aging in Human and Equine Asthma
Bullone, M., & Lavoie, J. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122612 · Cited by 72 · see citing works
Asthma Over the Age of 65: All's Well That Ends Well
Baptist, A. P., & Busse, P. J. (2018) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2018.02.007 · Cited by 71 · see citing works
Cellular senescence in lymphoid organs and immunosenescence
Budamagunta, V., Foster, T. C., & Zhou, D. (2021) · Aging · doi:10.18632/aging.203405 · Cited by 68 · see citing works
Zheng, J. H., & Perlman, S. M. (2017) · Current Opinion in Virology · doi:10.1016/j.coviro.2017.11.002 · Cited by 66 · see citing works
Self-citationSoliman, A. T., Nair, A. P., Masalamani, M. S. A., Sanctis, V. D., Khattab, M. A. A., Alsaud, A. E., Sasi, S., Ali, E. A., Hassan Ola, A., Iqbal, F. M., et al. (2020) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · doi:10.23750/abm.v91i3.10214 · Cited by 65 · see citing works
Aging, cancer, and antitumor immunity
Ikeda, H., & Togashi, Y. (2021) · International Journal of Clinical Oncology · doi:10.1007/s10147-021-01913-z · Cited by 65 · see citing works
Defending against SARS-CoV-2: The T cell perspective
Almendro-Vázquez, P., Laguna‐Goya, R., & Paz‐Artal, E. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1107803 · Cited by 64 · see citing works
Middle East respiratory syndrome coronavirus vaccines: current status and novel approaches
Okba, N. M. A., Raj, V. S., & Haagmans, B. L. (2017) · Current Opinion in Virology · doi:10.1016/j.coviro.2017.03.007 · Cited by 64 · see citing works
Immunosenescence and inflamm-ageing in COVID-19
Zinatizadeh, M. R., Zarandi, P. K., Ghiasi, M., Kooshki, H., Mohammadi, M., Amani, J., & Rezaei, N. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101818 · Cited by 62 · see citing works
Tincati, C., Cannizzo, E. S., Giacomelli, M., Badolato, R., Monforte, A. D., & Marchetti, G. C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.580987 · Cited by 61 · see citing works
Host Recovery from Respiratory Viral Infection
Wei, X., Narasimhan, H., Zhu, B., & Sun, J. (2023) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101921-040450 · Cited by 61 · see citing works
COVID-19: Immunology, Immunopathogenesis and Potential Therapies
Bhardwaj, A., Sapra, L., Saini, C., Azam, Z., Mishra, P. K., Verma, B., Mishra, G. C., & Srivastava, R. K. (2021) · International Reviews of Immunology · doi:10.1080/08830185.2021.1883600 · Cited by 61 · see citing works
Xu, Y., Qi, R.-Q., Chen, W.-B., Shi, Y., Cui, Z.-Z., Gao, X.-H., Chen, H.-D., Zhou, L., & Mi, Q. (2012) · Aging · doi:10.18632/aging.100501 · Cited by 59 · see citing works
Cellular and Humoral Immune Responses in Covid-19 and Immunotherapeutic Approaches
Hasan, A., Al‐Ozairi, E., Albaqsumi, Z., Ahmad, R., & Al‐Mulla, F. (2021) · ImmunoTargets and Therapy · doi:10.2147/itt.s280706 · Cited by 56 · see citing works
Reduced dynamic range of antiviral innate immune responses in aging
Molony, R. D., Malawista, A., & Montgomery, R. R. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.08.019 · Cited by 59 · see citing works
A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant
Agnihothram, S., Yount, B. L., Donaldson, E., Huynh, J., Menachery, V. D., Gralinski, L. E., Graham, R. L., Becker, M. M., Tomar, S., Scobey, T., et al. (2014) · mBio · doi:10.1128/mbio.00047-14 · Cited by 56 · see citing works
Middle East respiratory syndrome and severe acute respiratory syndrome
Vijay, R., & Perlman, S. M. (2016) · Current Opinion in Virology · doi:10.1016/j.coviro.2016.01.011 · Cited by 54 · see citing works
Self-citation
- Authors
- Zhao, J., Zhao, J., Legge, K., & Perlman, S.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Perlman, Stanley
- Venue
- Journal of Clinical Investigation
- Published
- 2011-12-01
- Volume
- 121
- Issue
- 12
- Pages
- 4921-4930
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3226008
- OpenAlex
- W2115101593
- Cited by
- 265
- References
- 60
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 8 · 2023: 15 · 2022: 26 · 2021: 42 · 2020: 66 · 2019: 5 · 2018: 10 · 2017: 12 · 2016: 14 · 2015: 9 · 2014: 15 · 2013: 16 · 2012: 6
- FWCI
- 5.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (PO1AI060699, AI060699, AI071085)
- National Institute of Allergy and Infectious Diseases (R01AI071085, R56 AI79424, R01AI091322, R56AI079424, P01AI060699)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- prostaglandin D2, dendritic cell migration, aging, respiratory viral infections, T cell response, draining lymph nodes, CCR7, chemokine receptors, age-related immunosenescence, lung immunity
- MeSH terms
- Aging, Animals, Cell Movement, Dendritic Cells, Disease Susceptibility, Murine hepatitis virus, Lung, Lymph Nodes, Lymphocyte Activation, Mice, Inbred C57BL, Orthomyxoviridae Infections, Influenza A virus, Prostaglandin Antagonists, Respiratory Syncytial Viruses, Specific Pathogen-Free Organisms, Prostaglandin D2, T-Lymphocyte Subsets, Immunocompromised Host, Coronavirus Infections, Respiratory Syncytial Virus Infections, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Mice, Receptors, CCR7, Cellular Microenvironment
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
