Role of dendritic cells in innate and adaptive immune response in human aging
Abstract
Aging is associated with a progressive decline in T cell function, chronic inflammation, hyperimmunoglobulinemia, autoimmunity, poor response to vaccines, and increased susceptibility to infection as well as diseases associated with chronic inflammation. DCs in aging appear to be functionally impaired with regard to response to uptake of antigens, phagocytosis of apoptotic cells, migration, priming of CD4+ and CD8+ T cells, and production of IFN-I and IFN-III. In this review I have discussed various mechanisms, which may be responsible for impaired functions of DCs.
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Circulating numbers, phenotypes, and costimulatory molecule expression of myeloid and plasmacytoid DCs appear intact in older individuals.
“Circulating numbers of myeloid and plasmacytoid DCs, their phenotypes, and their ability to express costimulatory molecules appear to be intact in older individuals”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Gupta, 2014
Myeloid DCs from older individuals have impaired ability to endocytose and present antigen to CD4+ and CD8+ T cells.
“myeloid (m)DCs from older individuals have impaired ability to endocytose and present antigen to CD4+ and CD8+ T cells”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Gupta, 2014
Type I IFN production in DCs from older individuals is reduced in vitro.
“type I IFN production in DCs from older individuals is reduced”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Gupta, 2014
Cites
Pathogen Recognition and Innate Immunity
Akira, S., Uematsu, S., & Takeuchi, O. (2006) · Cell · doi:10.1016/j.cell.2006.02.015 · Cited by 11,974 · see citing works
Immunobiology of Dendritic Cells
Banchereau, J., Brière, F., Caux, C., Davoust, J. M., Lebecque, S., Liu, Y., Pulendran, B., & Palucka, K. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.767 · Cited by 6,612 · see citing works
The Nature of the Principal Type 1 Interferon-Producing Cells in Human Blood
Siegal, F. P., Kadowaki, N., Shodell, M., Fitzgerald-Bocarsly, P. A., Shah, K., Ho, S., Antonenko, S., & Liu, Y.-J. (1999) · Science · doi:10.1126/science.284.5421.1835 · Cited by 2,293 · see citing works
Phenotypic plasticity and the epigenetics of human disease
Feinberg, A. P. (2007) · Nature · doi:10.1038/nature05919 · Cited by 1,613 · see citing works
Jego, G., Palucka, A. K., Blanck, J.-P., Chalouni, C., Pascual, V., & Banchereau, J. (2003) · Immunity · doi:10.1016/s1074-7613(03)00208-5 · Cited by 1,067 · see citing works
A Critical Role for IL-21 in Regulating Immunoglobulin Production
Ozaki, K., Spolski, R., Feng, C. G., Qi, C.-F., Cheng, J., Sher, A., Morse, H. C., Liu, C., Schwartzberg, P. L., & Leonard, W. J. (2002) · Science · doi:10.1126/science.1077002 · Cited by 978 · see citing works
(2006) · Elsevier eBooks · doi:10.1016/b978-0-12-595961-2.x5000-8 · Cited by 962 · see citing works
DNA Repair, Genome Stability, and Aging
Lombard, D. B., Chua, K. F., Mostoslavsky, R., Franco, S., Gostissa, M., & Alt, F. W. (2005) · Cell · doi:10.1016/j.cell.2005.01.028 · Cited by 944 · see citing works
Type I Interferons Keep Activated T Cells Alive
Marrack, P., Kappler, J. W., & Mitchell, T. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.3.521 · Cited by 763 · see citing works
Aging and proinflammatory cytokines
Bruunsgaard, H., Pedersen, M., & Pedersen, B. K. (2001) · Current Opinion in Hematology · doi:10.1097/00062752-200105000-00001 · Cited by 690 · see citing works
PTEN: Life as a Tumor Suppressor
Simpson, L., & Parsons, R. E. (2001) · Experimental Cell Research · doi:10.1006/excr.2000.5130 · Cited by 679 · see citing works
Increased cytokine production in mononuclear cells of healthy elderly people
Fagiolo, U., Cossarizza, A., Scala, E., Fanales‐Belasio, E., Ortolani, C., Cozzi, E., Monti, D., Franceschi, C., & Paganelli, R. (1993) · European Journal of Immunology · doi:10.1002/eji.1830230950 · Cited by 665 · see citing works
PI3K and negative regulation of TLR signaling
Fukao, T., & Koyasu, S. (2003) · Trends in Immunology · doi:10.1016/s1471-4906(03)00139-x · Cited by 612 · see citing works
Viral infection switches non-plasmacytoid dendritic cells into high interferon producers
Diebold, S. S., Montoya, M., Unger, H., Alexopoulou, L., Roy, P., Haswell, L. E., Al‐Shamkhani, A., Flavell, R. A., Borrow, P., & Sousa, C. R. E. (2003) · Nature · doi:10.1038/nature01783 · Cited by 582 · see citing works
Panda, A., Qian, F., Mohanty, S., van Duin, D., Newman, F. K., Zhang, L., Chen, S., Towle, V., Belshe, R. B., Fikrig, E., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0901022 · Cited by 548 · see citing works
The immunology of exceptional individuals: the lesson of centenarians
Franceschi, C., Monti, D., Sansoni, P., & Cossarizza, A. (1995) · Immunology Today · doi:10.1016/0167-5699(95)80064-6 · Cited by 531 · see citing works
DNA damage, cellular senescence and organismal ageing: causal or correlative?
Chen, J.-H., Hales, C. N., & Ozanne, S. E. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm681 · Cited by 481 · see citing works
Mordstein, M., Neugebauer, E., Ditt, V., Jessen, B., Rieger, T., Falcone, V., Sorgeloos, F., Ehl, S. R., Mayer, D., Kochs, G., et al. (2010) · Journal of Virology · doi:10.1128/jvi.00272-10 · Cited by 447 · see citing works
Agrawal, A., Agrawal, S., Cao, J.-N., Su, H., Osann, K., & Gupta, S. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.11.6912 · Cited by 435 · see citing works
Self-citationInterferons and viral infections
Fensterl, V., & Sen, G. C. (2009) · BioFactors · doi:10.1002/biof.6 · Cited by 396 · see citing works
Merad, M., & Manz, M. G. (2009) · Blood · doi:10.1182/blood-2008-12-180646 · Cited by 395 · see citing works
Type I Interferon Receptors: Biochemistry and Biological Functions
de Weerd, N. A., Samarajiwa, S., & Hertzog, P. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.r700006200 · Cited by 390 · see citing works
Altered cytokine production in the elderly
Rink, L., Cakman, I., & Kirchner, H. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(97)00153-x · Cited by 378 · see citing works
Bon, A. L., Thompson, C., Kamphuis, E., Durand, V., Rossmann, C., Kalinke, U., & Tough, D. F. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.4.2074 · Cited by 361 · see citing works
Schmitt, N., Morita, R., Bourdery, L., Bentebibel, S.-E., Zurawski, S., Banchereau, J., & Ueno, H. (2009) · Immunity · doi:10.1016/j.immuni.2009.04.016 · Cited by 357 · see citing works
Pawelec, G. (1998) · Frontiers in bioscience · doi:10.2741/a266 · Cited by 357 · see citing works
Plasmacytoid dendritic cells and type I IFN: 50 years of convergent history
Fitzgerald-Bocarsly, P. A., Dai, J., & Singh, S. (2008) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2007.10.006 · Cited by 351 · see citing works
Ma, C. S., Suryani, S., Avery, D. T., Chan, A., Nanan, R. K. H., Santner‐Nanan, B., Deenick, E. K., & Tangye, S. G. (2009) · Immunology and Cell Biology · doi:10.1038/icb.2009.64 · Cited by 345 · see citing works
Mordstein, M., Kochs, G., Dumoutier, L., Renauld, J., Paludan, S. R., Klucher, K. M., & Staeheli, P. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000151 · Cited by 326 · see citing works
The Role of Stat4 in Species-Specific Regulation of Th Cell Development by Type I IFNs
Rogge, L., D’Ambrosio, D., Biffi, M., Penna, G., Minetti, L. J., Presky, D. H., Adorini, L., & Sinigaglia, F. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.12.6567 · Cited by 298 · see citing works
Jing, Y., Shaheen, E., Drake, R. R., Chen, N., Gravenstein, S., & Deng, Y. (2009) · Human Immunology · doi:10.1016/j.humimm.2009.07.005 · Cited by 284 · see citing works
Peripheral blood dendritic cells and monocytes are differently regulated in the elderly
Bella, S. D., Bierti, L., Presicce, P., Arienti, R., Valenti, M., Saresella, M., Vergani, C., & Villa, M. L. (2006) · Clinical Immunology · doi:10.1016/j.clim.2006.09.012 · Cited by 280 · see citing works
IFN‐α/β enhances BCR‐dependent B cell responses
Braun, D., Caramalho, Í., & Demengeot, J. (2002) · International Immunology · doi:10.1093/intimm/14.4.411 · Cited by 269 · see citing works
Lambda Interferon Is the Predominant Interferon Induced by Influenza A Virus Infection In Vivo
Jewell, N. A., Cline, T. D., Mertz, S. E., Sv, S., Flaño, E., Schindler, C., Grieves, J. L., Durbin, R. K., Kotenko, S. V., & Durbin, J. E. (2010) · Journal of Virology · doi:10.1128/jvi.01703-09 · Cited by 263 · see citing works
Structural basis of a unique interferon-β signaling axis mediated via the receptor IFNAR1
de Weerd, N. A., Vivian, J. P., Nguyen, T. K., Mangan, N. E., Gould, J. A., Braniff, S.-J., Zaker-Tabrizi, L., Fung, K. Y., Forster, S. C., Beddoe, T., et al. (2013) · Nature Immunology · doi:10.1038/ni.2667 · Cited by 260 · see citing works
Martin, M., Schifferle, R. E., Cuesta, N., Vogel, S. N., Katz, J., & Michalek, S. M. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.2.717 · Cited by 259 · see citing works
Aggarwal, S., Gollapudi, S. V. S., & Gupta, S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.4.2154 · Cited by 252 · see citing works
Self-citationInterferon Induced IFIT Family Genes in Host Antiviral Defense
Zhou, X., Michal, J. J., Zhang, L., Ding, B., Lunney, J. K., Liu, B., & Jiang, Z. (2013) · International Journal of Biological Sciences · doi:10.7150/ijbs.5613 · Cited by 247 · see citing works
Shigematsu, H., Reizis, B., Iwasaki, H., Mizuno, S.-I., Hu, D., Traver, D. J., Leder, P., Sakaguchi, N., & Akashi, K. (2004) · Immunity · doi:10.1016/j.immuni.2004.06.011 · Cited by 239 · see citing works
Aggarwal, S., Gollapudi, S., & Gupta, S. (1999) · PubMed · Cited by 231 · see citing works
Self-citationAggarwal, S., & Gupta, S. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.4.1627 · Cited by 229 · see citing works
Self-citationRole of DNA Methylation in the Regulation of Cell Function: Autoimmunity, Aging and Cancer
Richardson, B. C. (2002) · Journal of Nutrition · doi:10.1093/jn/132.8.2401s · Cited by 204 · see citing works
Thymus and aging: morphological, radiological, and functional overview
Rezzani, R., Nardo, L., Favero, G., Peroni, M., & Rodella, L. F. (2013) · AGE · doi:10.1007/s11357-013-9564-5 · Cited by 198 · see citing works
Circulating, Interferon‐Producing Plasmacytoid Dendritic Cells Decline During Human Ageing
Shodell, M., & Siegal, F. P. (2002) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.2002.01148.x · Cited by 189 · see citing works
Type I Interferon as a Link Between Innate and Adaptive Immunity through Dendritic Cell Stimulation
Tough, D. F. (2003) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/1042819031000149368 · Cited by 188 · see citing works
Age-related epigenetic changes and the immune system
Issa, J. J. (2003) · Clinical Immunology · doi:10.1016/s1521-6616(03)00203-1 · Cited by 181 · see citing works
RECIPROCAL CHANGE WITH AGE IN ANTIBODY TO EXTRINSIC AND INTRINSIC ANTIGENS
Rowley, M. J., Buchanan, H., & Mackay, I. R. (1968) · The Lancet · doi:10.1016/s0140-6736(68)92893-6 · Cited by 170 · see citing works
Harnessing human dendritic cell subsets for medicine
Ueno, H., Schmitt, N., Klechevsky, E., Pedroza‐González, A., Matsui, T., Zurawski, G., Oh, S., Fay, J. W., Pascual, V., Banchereau, J., et al. (2010) · Immunological Reviews · doi:10.1111/j.0105-2896.2009.00884.x · Cited by 166 · see citing works
Increased Reactivity of Dendritic Cells from Aged Subjects to Self-Antigen, the Human DNA
Agrawal, A., Tay, J., Ton, S., Agrawal, S., & Gupta, S. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.182.2.1138 · Cited by 165 · see citing works
Self-citationSridharan, A., Esposo, M., Kaushal, K., Tay, J., Osann, K., Agrawal, S., Gupta, S., & Agrawal, A. (2011) · AGE · doi:10.1007/s11357-010-9191-3 · Cited by 165 · see citing works
Self-citationLung, T. L., Saurwein-Teissl, M., Parson, W., Schönitzer, D., & Grubeck-Loebenstein, B. (2000) · Vaccine · doi:10.1016/s0264-410x(99)00494-6 · Cited by 161 · see citing works
ENZYMATIC OR PHARMACOLOGICAL FIBRINOLYSIS?
Marshall, M. (1964) · PubMed · Cited by 154 · see citing works
Steger, M. M., Maczek, C., & Grubeck-Loebenstein, B. (1996) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1996.d01-790.x · Cited by 138 · see citing works
Type III IFNs: New layers of complexity in innate antiviral immunity
Ank, N., & Paludan, S. R. (2009) · BioFactors · doi:10.1002/biof.19 · Cited by 97 · see citing works
Tomer, Y., & Shoenfeld, Y. (1988) · Autoimmunity · doi:10.3109/08916938809001927 · Cited by 97 · see citing works
Influenza-Induced Production of Interferon-Alpha is Defective in Geriatric Individuals
Canaday, D. H., Amponsah, N. A., Jones, L., Tisch, D. J., Hornick, T. R., & Ramachandra, L. (2010) · Journal of Clinical Immunology · doi:10.1007/s10875-010-9374-9 · Cited by 89 · see citing works
Molecular mechanisms of apoptosis in the cells of the immune system in human aging
Gupta, S. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00261.x · Cited by 85 · see citing works
Age-associated epigenetic modifications in human DNA increase its immunogenicity
Agrawal, A., Tay, J., Yang, G., Agrawal, S., & Gupta, S. (2010) · Aging · doi:10.18632/aging.100121 · Cited by 84 · see citing works
Self-citationImpaired secretion of interferons by dendritic cells from aged subjects to influenza
Prakash, S., Agrawal, S., Cao, J., Gupta, S., & Agrawal, A. (2012) · AGE · doi:10.1007/s11357-012-9477-8 · Cited by 80 · see citing works
Self-citationReduced numbers of plasmacytoid dendritic cells in aged blood donors
Pérez-Cabezas, B., Naranjo-Gómez, M., Fernández, M. A., Grífols, J. R., Pujol-Borrell, R., & Borràs, F. E. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2007.05.010 · Cited by 80 · see citing works
Age‐Related Changes in Human Blood Dendritic Cell Subpopulations
Teig, N., Moses, D. C., Gieseler, S., & Schauer, U. (2002) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.2002.01068.x · Cited by 78 · see citing works
Molecular Steps of Cell Suicide: An Insight into Immune Senescence
Gupta, S. (2000) · Journal of Clinical Immunology · doi:10.1023/a:1006653917314 · Cited by 66 · see citing works
Self-citationAge-related decline of human interferon alpha and interferon gamma production
Abb, J., Abb, H., & Deinhardt, F. W. (1984) · Blut Zeitschrift für die gesamte Blutforschung · doi:10.1007/bf00320399 · Cited by 61 · see citing works
Weksler, M. E., & Goodhardt, M. (2002) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00091-8 · Cited by 54 · see citing works
Acquisition of Oxidative DNA Damage during Senescence
Martien, S., & Abbadie, C. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1404.010 · Cited by 50 · see citing works
Type I interferons promote cross-priming: more functions for old cytokines
Beignon, A., Škoberne, M., & Bhardwaj, N. (2003) · Nature Immunology · doi:10.1038/ni1003-939 · Cited by 50 · see citing works
Increased activation and cytokine secretion in B cells stimulated with leptin in aged humans
Gupta, S., Agrawal, S., & Gollapudi, S. V. S. (2013) · Immunity & Ageing · doi:10.1186/1742-4933-10-3 · Cited by 41 · see citing works
Self-citationDirecting Autoimmunity to Nucleoprotein Particles
Hardin, J. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030130 · Cited by 39 · see citing works
Agrawal, A., Su, H., Chen, J., Osann, K., Agrawal, S., & Gupta, S. (2012) · Aging · doi:10.18632/aging.100490 · Cited by 35 · see citing works
Self-citationAgeing impairs the T cell response to dendritic cells
You, J., Dong, H., Mann, E. R., Knight, S. C., & Yaqoob, P. (2013) · Immunobiology · doi:10.1016/j.imbio.2013.02.002 · Cited by 28 · see citing works
Shoshan, Y., & Mevorach, D. (2004) · Autoimmunity · doi:10.1080/08916930410001666622 · Cited by 21 · see citing works
Wagner, U. G. (2011) · Springer eBooks · doi:10.1007/978-3-0346-0219-8_7 · Cited by 9 · see citing works
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- Authors
- Gupta, S.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Gupta, Sudhir
- ORCID
- Gupta, Sudhir
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 54
- Pages
- 47-52
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2057623513
- Cited by
- 80
- References
- 72
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 8 · 2023: 8 · 2022: 10 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 11 · 2017: 8 · 2016: 4 · 2015: 5 · 2014: 2
- FWCI
- 0.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- dendritic cells, aging, innate immunity, adaptive immunity, T cell function, chronic inflammation, immunosenescence, phagocytosis of apoptotic cells, dendritic cell migration, T cell priming, type I interferon, vaccine response, autoimmunity
- MeSH terms
- Aging, Dendritic Cells, Disease Susceptibility, DNA, Humans, Hypergammaglobulinemia, Immunity, Innate, Autoimmunity, Cytokines, Adaptive Immunity
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