Human immune system variation
Open accessAbstract
The human immune system is highly variable between individuals but relatively stable over time within a given person. Recent conceptual and technological advances have enabled systems immunology analyses, which reveal the composition of immune cells and proteins in populations of healthy individuals. The range of variation and some specific influences that shape an individual's immune system is now becoming clearer. Human immune systems vary as a consequence of heritable and non-heritable influences, but symbiotic and pathogenic microbes and other non-heritable influences explain most of this variation. Understanding when and how such influences shape the human immune system is key for defining metrics of immunological health and understanding the risk of immune-mediated and infectious diseases.
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Factors such as age, sex, circadian rhythm, host-commensal interactions, seasonal changes, and fitness substantially affect interindividual variation of the immune response.
“Whilst within the individual this remains relatively stable over time, factors such as age, sex, circadian rhythm, host–commensal interactions, seasonal changes, and fitness have shown to substantially affect interindividual variation of the immune response.[ 26 ]”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [26]
The sections on variation with age, variation by sex, and influences of the microbiota describe factors shaping immune systems; the seasonal and circadian section also describes changes over time. But those time-dependent findings do not establish substantial differences between individuals, the paper calls the effects of age and sex on immune profiles “often subtle,” and no passage found supports fitness as a factor (searched: fitness, physical activity, exercise). Page numbers were not available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe neonatal innate immune system comprises different protective cell populations compared with adults, as well as qualitative differences in the responses by shared cell populations.
“The neonatal innate immune system comprises different protective cell populations compared with adults, as well as qualitative differences in the responses by shared cell populations [23].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [23]
Autoimmune disorders such as Sjogren syndrome, systemic lupus erythematosus and autoimmune thyroid disease are higher in women.
“autoimmune disorders such as Sjogren syndrome, systemic lupus erythematosus and autoimmune thyroid disease are higher in women [23].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [23]
Infants and young children are more susceptible to infections than adolescents and adults.
“These factors, combined with their greater potential for exposure to pathogens at nursery and school, means that infants and young children are more susceptible to infections than adolescents and adults [23].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [23]
In older people, a lifetime of exposure to antigens and to numerous sources of oxidative stress can cause immune dysregulation that makes them more susceptible to infections than any other age group apart from young children.
“In older people, a lifetime of exposure to antigens and to numerous sources of oxidative stress can cause immune dysregulation that makes them more susceptible to infections than any other age group apart from young children [23,35,36].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [23]
It is especially important to ensure that antioxidant levels (e.g., vitamins C, E, and A) and micronutrients that are components of antioxidant enzymes (e.g., zinc, copper, iron, and selenium) are sufficient to combat the oxidative stress that is induced by many lifestyle factors common in this group, and which has great impact on immune function.
“It is especially important to ensure that antioxidant levels (e.g., vitamins C, E, and A) and micronutrients that are components of antioxidant enzymes (e.g., zinc, copper, iron, and selenium) are sufficient to combat the oxidative stress that is induced by many lifestyle factors common in this group, and which has great impact on immune function [10,23,35,36,44].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [23]
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Cites
Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets.
Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.002 · Cited by 7,110 · see citing works
Hay fever, hygiene, and household size.
Strachan, D. P. (1989) · BMJ · doi:10.1136/bmj.299.6710.1259 · Cited by 5,054 · see citing works
Commensal <i>Bifidobacterium</i> promotes antitumor immunity and facilitates anti–PD-L1 efficacy
Sivan, A., Corrales, L., Hubert, N., Williams, J. B., Aquino-Michaels, K., Earley, Z. M., Benyamin, F. W., Man Lei, Y., Jabri, B., Alegre, M.-L., et al. (2015) · Science · doi:10.1126/science.aac4255 · Cited by 3,888 · see citing works
Epigenetic differences arise during the lifetime of monozygotic twins
Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., Heine-Suñer, D., Cigudosa, J. C., Urioste, M., Benitez, J., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500398102 · Cited by 3,602 · see citing works
Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota
Vétizou, M., Pitt, J. M., Daillère, R., Lepage, P., Waldschmitt, N., Flament, C., Rusakiewicz, S., Routy, B., Roberti, M. P., Duong, C. P. M., et al. (2015) · Science · doi:10.1126/science.aad1329 · Cited by 3,488 · see citing works
The effect of infections on susceptibility to autoimmune and allergic diseases.
Bach, J. (2002) · New England Journal of Medicine · doi:10.1056/nejmra020100 · Cited by 2,714 · see citing works
Bendall, S. C., Simonds, E. F., Qiu, P., Amir, E.-A. D., Krutzik, P. O., Finck, R., Bruggner, R. V., Melamed, R., Trejo, A., Ornatsky, O. I., et al. (2011) · Science · doi:10.1126/science.1198704 · Cited by 2,279 · see citing works
Baechler, E. C., Batliwalla, F., Karypis, G., Gaffney, P. M., Ortmann, W. A., Espe, K. J., Shark, K. B., Grande, W. J., Hughes, K. M. H., Kapur, V., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0337679100 · Cited by 2,246 · see citing works
The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide
Viaud, S., Saccheri, F., Mignot, G., Yamazaki, T., Daillère, R., Hannani, D., Enot, D. P., Pfirschke, C., Engblom, C., Pittet, M. J., et al. (2013) · Science · doi:10.1126/science.1240537 · Cited by 2,050 · see citing works
How colonization by microbiota in early life shapes the immune system
Gensollen, T., Iyer, S. S., Kasper, D. L., & Blumberg, R. S. (2016) · Science · doi:10.1126/science.aad9378 · Cited by 2,044 · see citing works
Environmental Exposure to Endotoxin and Its Relation to Asthma in School-Age Children
Braun‐Fahrländer, C., Riedler, J., Herz, U., Eder, W., Waser, M., Grize, L., Maisch, S., Carr, D., Gerlach, F., Bufe, A., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020057 · Cited by 1,810 · see citing works
Evolution of the immune system in humans from infancy to old age
Simon, A. K., Hollander, G. A., & McMichael, A. (2015) · Proceedings of the Royal Society B: Biological Sciences · doi:10.1098/rspb.2014.3085 · Cited by 1,796 · see citing works
Early infancy microbial and metabolic alterations affect risk of childhood asthma
Arrieta, M., Stiemsma, L. T., Dimitriu, P. A., Thorson, L., Russell, S., Yurist‐Doutsch, S., Kuzeljevic, B., Gold, M. J., Britton, H. M., Lefebvre, D. L., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aab2271 · Cited by 1,783 · see citing works
Sylwester, A. W., Mitchell, B. L., Edgar, J. B., Taormina, C., Pelte, C., Ruchti, F., Sleath, P. R., Grabstein, K. H., Hosken, N. A., Kern, F., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050882 · Cited by 1,339 · see citing works
Bandura, D. R., Baranov, V. I., Ornatsky, O. I., Antonov, A., Kinach, R., Lou, X., Pavlov, S., Vorobiev, S., Dick, J. E., & Tanner, S. D. (2009) · Analytical Chemistry · doi:10.1021/ac901049w · Cited by 1,295 · see citing works
Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans
Vatanen, T., Kostic, A. D., d’Hennezel, E., Siljander, H., Franzosa, E. A., Yassour, M., Kolde, R., Vlamakis, H., Arthur, T. D., Hämäläinen, A.-M., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.007 · Cited by 1,289 · see citing works
Sex differences in autoimmune disease
Whitacre, C. C. (2001) · Nature Immunology · doi:10.1038/ni0901-777 · Cited by 1,271 · see citing works
Gut immune maturation depends on colonization with a host-specific microbiota
Chung, H., Pamp, S. J., Hill, J. A., Surana, N. K., Edelman, S. M., Troy, E. B., Reading, N. C., Villablanca, E. J., Wang, S., Mora, J. R., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.037 · Cited by 1,241 · see citing works
Effects of cigarette smoke on the immune system
Sopori, M. L. (2002) · Nature reviews. Immunology · doi:10.1038/nri803 · Cited by 1,219 · see citing works
Mass Cytometry: Single Cells, Many Features
Spitzer, M. H., & Nolan, G. P. (2016) · Cell · doi:10.1016/j.cell.2016.04.019 · Cited by 1,199 · see citing works
Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans
Querec, T. D., Akondy, R. S., Lee, E. K., Cao, W., Nakaya, H. I., Teuwen, D. E., Pirani, A. M., Gernert, K. M., Deng, J., Marzolf, B., et al. (2008) · Nature Immunology · doi:10.1038/ni.1688 · Cited by 1,123 · see citing works
Proinflammatory Cytokines, Aging, and Age-Related Diseases
Michaud, M., Balardy, L., Moulis, G., Gaudin, C., Peyrot, C., Vellas, B., Cesari, M., & Nourhashemi, F. (2013) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2013.05.009 · Cited by 1,094 · see citing works
Normalizing the environment recapitulates adult human immune traits in laboratory mice
Beura, L. K., Hamilton, S. E., Bi, K., Schenkel, J. M., Odumade, O. A., Casey, K. A., Thompson, E. A., Fraser, K. A., Rosato, P. C., Filali-Mouhim, A., et al. (2016) · Nature · doi:10.1038/nature17655 · Cited by 1,072 · see citing works
Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences
Brodin, P., Jojic, V., Gao, T., Bhattacharya, S., Angel, C. J. L., Furman, D., Shen-Orr, S., Dekker, C. L., Swan, G. E., Butte, A. J., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.020 · Cited by 1,065 · see citing works
Self-citationRapid cloning of high-affinity human monoclonal antibodies against influenza virus
Wrammert, J., Smith, K., Miller, J., Langley, W. A., Kokko, K. E., Larsen, C. P., Zheng, N., Mays, I., Garman, L., Helms, C., et al. (2008) · Nature · doi:10.1038/nature06890 · Cited by 1,026 · see citing works
Genetic and Environmental Influences on Premature Death in Adult Adoptees
Sørensen, T. I. A., Nielsen, G. G., Andersen, P. K., & Teasdale, T. W. (1988) · New England Journal of Medicine · doi:10.1056/nejm198803243181202 · Cited by 823 · see citing works
ImmPort: disseminating data to the public for the future of immunology
Bhattacharya, S., Andorf, S., Gomes, L., Dunn, P. J., Schaefer, H., Pontius, J. U., Berger, P., Desborough, V., Smith, T., Campbell, J. P., et al. (2014) · Immunologic Research · doi:10.1007/s12026-014-8516-1 · Cited by 807 · see citing works
Individuality and variation in gene expression patterns in human blood
Whitney, A. R., Diehn, M., Popper, S. J., Alizadeh, A. A., Boldrick, J. C., Relman, D. A., & Brown, P. O. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252784499 · Cited by 775 · see citing works
Diversity and clonal selection in the human T-cell repertoire
Qi, Q., Liu, Y., Cheng, Y., Glanville, J., Zhang, D., Lee, J.-Y., Olshen, R. A., Weyand, C. M., Boyd, S. D., & Goronzy, J. J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409155111 · Cited by 755 · see citing works
Lundberg, M., Eriksson, A., Tran, B., Assarsson, E., & Fredriksson, S. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr424 · Cited by 744 · see citing works
Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients
Banchereau, R., Hong, S., Cantarel, B. L., Baldwin, N. E., Baisch, J. M., Edens, M., Cepika, A., Acs, P., Turner, J., Anguiano, E., et al. (2016) · Cell · doi:10.1016/j.cell.2016.03.008 · Cited by 735 · see citing works
Padyukov, L., Silva, C., Stolt, P., Alfredsson, L. S., & Klareskog, L. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20553 · Cited by 681 · see citing works
Furman, D., Hejblum, B. P., Simon, N., Jojic, V., Dekker, C. L., Thiébaut, R., Tibshirani, R. J., & Davis, M. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321060111 · Cited by 678 · see citing works
Self-citationCircadian Clock Proteins and Immunity
Curtis, A. M., Bellet, M. M., Sassone‐Corsi, P., & O'Neill, L. A. J. (2014) · Immunity · doi:10.1016/j.immuni.2014.02.002 · Cited by 644 · see citing works
Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation
Jenq, R. R., Ubeda, C., Taur, Y., Menezes, C. C., Khanin, R., Dudakov, J. A., Liu, C., West, M. L., Singer, N. V., Equinda, M. J., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20112408 · Cited by 626 · see citing works
The Virome in Mammalian Physiology and Disease
Virgin, H. W. (2014) · Cell · doi:10.1016/j.cell.2014.02.032 · Cited by 598 · see citing works
Newell, E. W., Sigal, N., Bendall, S. C., Nolan, G. P., & Davis, M. M. (2012) · Immunity · doi:10.1016/j.immuni.2012.01.002 · Cited by 555 · see citing works
Self-citationMultiplexed mass cytometry profiling of cellular states perturbed by small-molecule regulators
Bodenmiller, B., Zunder, E. R., Finck, R., Chen, T. J., Savig, E. S., Bruggner, R. V., Simonds, E. F., Bendall, S. C., Sachs, K., Krutzik, P. O., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2317 · Cited by 546 · see citing works
Heritability of Cardiovascular and Personality Traits in 6,148 Sardinians
Pilia, G., Chen, W., Scuteri, A., Orrù, M., Albai, G., Dei, M., Lai, S., Usala, G., Lai, M., Loi, P., et al. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020132 · Cited by 543 · see citing works
Oh, J. Z., Ravindran, R., Chassaing, B., Carvalho, F. A., Maddur, M. S., Bower, M., Hakimpour, P., Gill, K. P., Nakaya, H. I., Yarovinsky, F., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.08.009 · Cited by 541 · see citing works
Widespread seasonal gene expression reveals annual differences in human immunity and physiology
Dopico, X. C., Evangelou, M., Ferreira, R. C., Guo, H., Pękalski, M. Ł., Smyth, D. J., Cooper, N., Burren, O. S., Fulford, A. J. C., Hennig, B. J., et al. (2015) · Nature Communications · doi:10.1038/ncomms8000 · Cited by 538 · see citing works
Linking T-cell receptor sequence to functional phenotype at the single-cell level
Han, A. S., Glanville, J., Hansmann, L., & Davis, M. M. (2014) · Nature Biotechnology · doi:10.1038/nbt.2938 · Cited by 534 · see citing works
Self-citationComprehensive serological profiling of human populations using a synthetic human virome
Xu, G. J., Kula, T., Xu, Q., Li, M. Z., Vernon, S. D., Ndung’u, T., Ruxrungtham, K., Sánchez, J., Brander, C., Chung, R. T., et al. (2015) · Science · doi:10.1126/science.aaa0698 · Cited by 478 · see citing works
Temporal Response of the Human Virome to Immunosuppression and Antiviral Therapy
De Vlaminck, I., Khush, K. K., Strehl, C., Kohli, B., Luikart, H., Neff, N. F., Okamoto, J., Snyder, T. M., Cornfield, D. N., Nicolls, M. R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.034 · Cited by 471 · see citing works
Global Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses
Tsang, J. S., Schwartzberg, P. L., Kotliarov, Y., Biancotto, A., Xie, Z., Germain, R. N., Wang, E., Olnes, M. J., Narayanan, M., Golding, H., et al. (2014) · Cell · doi:10.1016/j.cell.2014.03.031 · Cited by 454 · see citing works
Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells
Lee, M. N., Ye, C., Villani, A.-C., Raj, T., Li, W., Eisenhaure, T. M., Imboywa, S. H., Chipendo, P. I., Ran, F. A., Slowikowski, K., et al. (2014) · Science · doi:10.1126/science.1246980 · Cited by 441 · see citing works
T cell fate and clonality inference from single-cell transcriptomes
(2016) · doi:10.1038/nmeth.3800 · Cited by 434 · see citing works
High serum IFN-α activity is a heritable risk factor for systemic lupus erythematosus
Niewold, T. B., Hua, J., Lehman, T. J. A., Harley, J. B., & Crow, M. K. (2007) · Genes and Immunity · doi:10.1038/sj.gene.6364408 · Cited by 417 · see citing works
Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity
Cutolo, M., Sulli, A., Capellino, S., Villaggio, B., Montagna, P., SERIOLO, B., & Straub, R. H. (2004) · Lupus · doi:10.1191/0961203304lu1094oa · Cited by 407 · see citing works
Ontogeny of early life immunity
Dowling, D. J., & Levy, O. (2014) · Trends in Immunology · doi:10.1016/j.it.2014.04.007 · Cited by 365 · see citing works
A Prescription for Human Immunology
Davis, M. M. (2008) · Immunity · doi:10.1016/j.immuni.2008.12.003 · Cited by 346 · see citing works
Self-citationRecent Advances in the Genetics of Autoimmune Disease
Gregersen, P. K., & Olsson, L. M. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132653 · Cited by 337 · see citing works
Nakaya, H. I., Hagan, T., Duraisingham, S. S., Lee, E. K., Kwissa, M., Rouphael, N., Frasca, D., Gersten, M., Mehta, A. K., Gaujoux, R., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.11.012 · Cited by 337 · see citing works
Lineage Structure of the Human Antibody Repertoire in Response to Influenza Vaccination
Jiang, N., He, J., Weinstein, J. A., Penland, L., Sasaki, S., He, X.-S., Dekker, C. L., Zheng, N.-Y., Huang, M., Sullivan, M., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3004794 · Cited by 335 · see citing works
Self-citationCytomegalovirus infection enhances the immune response to influenza
Furman, D., Jojic, V., Sharma, S., Shen-Orr, S. S., L. Angel, C. J., Onengut-Gumuscu, S., Kidd, B. A., Maecker, H. T., Concannon, P., Dekker, C. L., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa2293 · Cited by 332 · see citing works
Self-citationGenetic Variants Regulating Immune Cell Levels in Health and Disease
Orrù, V., Steri, M., Sole, G., Sidore, C., Virdis, F., Dei, M., Lai, S., Żołędziewska, M., Busonero, F., Mulas, A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.08.041 · Cited by 330 · see citing works
Highly multiplexed simultaneous detection of RNAs and proteins in single cells
Frei, A. P., Bava, F.-A., Zunder, E. R., Hsieh, E. W. Y., Chen, S.-Y., Nolan, G. P., & Gherardini, P. F. (2016) · Nature Methods · doi:10.1038/nmeth.3742 · Cited by 330 · see citing works
The cellular composition of the human immune system is shaped by age and cohabitation
Carr, E. J., Dooley, J., Garcia‐Perez, J. E., Lagou, V., Lee, J. C., Wouters, C. H., Meyts, I., Goris, A., Boeckxstaens, G. E., Linterman, M. A., et al. (2016) · Nature Immunology · doi:10.1038/ni.3371 · Cited by 308 · see citing works
Roederer, M., Quaye, L., Mangino, M., Beddall, M. H., Mahnke, Y., Chattopadhyay, P., Tosi, I., Napolitano, L., Terranova Barberio, M., Menni, C., et al. (2015) · Cell · doi:10.1016/j.cell.2015.02.046 · Cited by 296 · see citing works
NK cell education: not an on-off switch but a tunable rheostat
Brodin, P., Kärre, K., & Höglund, P. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.01.006 · Cited by 285 · see citing works
Self-citationSystemic lupus erythematosus: all roads lead to type I interferons
Pascual, V., Farkas, L., & Banchereau, J. (2006) · Current Opinion in Immunology · doi:10.1016/j.coi.2006.09.014 · Cited by 285 · see citing works
The human model: a genetic dissection of immunity to infection in natural conditions
Casanova, J., & Abel, L. (2004) · Nature reviews. Immunology · doi:10.1038/nri1264 · Cited by 277 · see citing works
Are there gender differences in severity of ankylosing spondylitis? Results from the PSOAS cohort
Lee, W., Reveille, J. D., Davis, J. C., Learch, T. J., Ward, M. M., & Weisman, M. H. (2006) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2006.060293 · Cited by 273 · see citing works
Low natural killer‐cell activity and immunoglobulin levels associated with smoking in human subjects
Ferson, M. J., Edwards, A., Lind, A., Milton, G. W., & Hersey, P. (1979) · International Journal of Cancer · doi:10.1002/ijc.2910230504 · Cited by 271 · see citing works
Straub, R. H., & Cutolo, M. (2007) · Arthritis & Rheumatism · doi:10.1002/art.22368 · Cited by 262 · see citing works
Reese, T. A., Bi, K., Kambal, A., Filali-Mouhim, A., Beura, L. K., Bürger, M. C., Pulendran, B., Sekaly, R.-P., Jameson, S. C., Masopust, D., et al. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.04.003 · Cited by 246 · see citing works
Intersection of population variation and autoimmunity genetics in human T cell activation
Ye, C. J., Feng, T., Kwon, H.-K., Raj, T., Wilson, M. T., Asinovski, N., McCabe, C., Lee, M. H., Frohlich, I., Paik, H.-I., et al. (2014) · Science · doi:10.1126/science.1254665 · Cited by 236 · see citing works
Grossman, Z., & Paul, W. E. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.21.10365 · Cited by 228 · see citing works
Epigenome-wide Association Studies and the Interpretation of Disease -Omics
Birney, E., Smith, G. D., & Greally, J. M. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006105 · Cited by 223 · see citing works
Seasonal variation of diagnosis of Type 1 diabetes mellitus in children worldwide
Moltchanova, E. V., Schreier, N., Lammi, N., & Karvonen, M. (2009) · Diabetic Medicine · doi:10.1111/j.1464-5491.2009.02743.x · Cited by 217 · see citing works
Goronzy, J. J., & Weyand, C. M. (2003) · Arthritis Research · doi:10.1186/ar974 · Cited by 199 · see citing works
Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants
Gibbons, D. L., Fleming, P., Virasami, A. K., Michel, M., Sebire, N. J., Costeloe, K., Carr, R. A., Klein, N. J., & Hayday, A. (2014) · Nature Medicine · doi:10.1038/nm.3670 · Cited by 196 · see citing works
Price, A. L., Helgason, A., Þorleifsson, G., McCarroll, S. A., Kong, A., & Stefánsson, K. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001317 · Cited by 195 · see citing works
The microbial basis of inflammatory bowel diseases
Dalal, S. R., & Chang, E. B. (2014) · Journal of Clinical Investigation · doi:10.1172/jci72330 · Cited by 195 · see citing works
Han, A. S., Newell, E. W., Glanville, J., Fernandez‐Becker, N., Khosla, C., Chien, Y., & Davis, M. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1311861110 · Cited by 194 · see citing works
Self-citationApoptosis and other immune biomarkers predict influenza vaccine responsiveness
Furman, D., Jojic, V., Kidd, B., Shen‐Orr, S., Price, J., Jarrell, J., Tse, T., Huang, H., Lund, P., Maecker, H. T., et al. (2013) · Molecular Systems Biology · doi:10.1038/msb.2013.15 · Cited by 184 · see citing works
Self-citationLife‐threatening infectious diseases of childhood: single‐gene inborn errors of immunity?
Alcaïs, A., Quintana‐Murci, L., Thaler, D. S., Schurr, E., Abel, L., & Casanova, J. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05834.x · Cited by 180 · see citing works
Enroth, S., Johansson, Å., Enroth, S. B., & Gyllensten, U. B. (2014) · Nature Communications · doi:10.1038/ncomms5684 · Cited by 176 · see citing works
Andres-Terrè, M., McGuire, H. M., Pouliot, Y., Bongen, E., Sweeney, T. E., Tato, C. M., & Khatri, P. (2015) · Immunity · doi:10.1016/j.immuni.2015.11.003 · Cited by 172 · see citing works
Ráki, M., Fallang, L.-E., Brottveit, M., Bergseng, E., Quarsten, H., Lundin, K. E. A., & Sollid, L. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608610104 · Cited by 156 · see citing works
Shen-Orr, S. S., Furman, D., Kidd, B. A., Hadad, F., Lovelace, P., Huang, Y.-W., Rosenberg-Hasson, Y., Mackey, S., Grisar, F. A. G., Pickman, Y., et al. (2016) · Cell Systems · doi:10.1016/j.cels.2016.09.009 · Cited by 154 · see citing works
Self-citationSobolev, O., Binda, E., O’Farrell, S., Lorenc, A., Pradines, J., Huang, Y., Duffner, J. L., Schulz, R., Cason, J. W., Zambon, M. C. F. A., et al. (2016) · Nature Immunology · doi:10.1038/ni.3328 · Cited by 149 · see citing works
Neonates harbour highly active γδ T cells with selective impairments in preterm infants
Gibbons, D. L., Haque, S. F. Y., Silberzahn, T., Hamilton, K., Langford, C., Ellis, P., Carr, R. A., & Hayday, A. (2009) · European Journal of Immunology · doi:10.1002/eji.200939222 · Cited by 145 · see citing works
Circadian rhythms in arthritis: Hormonal effects on the immune/inflammatory reaction
Cutolo, M., & Straub, R. H. (2007) · Autoimmunity Reviews · doi:10.1016/j.autrev.2007.11.019 · Cited by 135 · see citing works
Immunotherapy: Bewitched, Bothered, and Bewildered No More
Steinman, R. M., & Mellman, I. (2004) · Science · doi:10.1126/science.1099688 · Cited by 135 · see citing works
Higuchi, T., Omata, F., TSUCHIHASHI, K., Higashioka, K., Koyamada, R., & Okada, S. (2016) · Preventive Medicine Reports · doi:10.1016/j.pmedr.2016.08.009 · Cited by 128 · see citing works
Systems vaccinology: Enabling rational vaccine design with systems biological approaches
Hagan, T., Nakaya, H. I., Subramaniam, S., & Pulendran, B. (2015) · Vaccine · doi:10.1016/j.vaccine.2015.03.072 · Cited by 127 · see citing works
Multiple Loci Are Associated with White Blood Cell Phenotypes
Nalls, M. A., Couper, D. J., Tanaka, T., van Rooij, F. J. A., Chen, M., Smith, A. V., Toniolo, D., Zakai, N. A., Yang, Q., Greinacher, A., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002113 · Cited by 123 · see citing works
Immune Adaptation to Environmental Influence: The Case of NK Cells and HCMV
Rölle, A., & Brodin, P. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.01.005 · Cited by 106 · see citing works
Self-citationvon Herrath, M. G., & Nepom, G. T. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051224 · Cited by 101 · see citing works
Cytokine genes and disease susceptibility
Ollier, W. (2004) · Cytokine · doi:10.1016/j.cyto.2004.07.014 · Cited by 96 · see citing works
What's in season for rheumatoid arthritis patients? Seasonal fluctuations in disease activity
Iikuni, N., Nakajima, A., Inoue, E., et al. (2007) · Lara D. Veeken · doi:10.1093/rheumatology/kel414 · Cited by 93 · see citing works
Mathews, J. D. (1973) · The Lancet · doi:10.1016/s0140-6736(73)91037-4 · Cited by 87 · see citing works
Replication of celiac disease UK genome-wide association study results in a US population
Garner, C., Murray, J. A., Ding, Y. C., Tien, Z., van Heel, D. A., & Neuhausen, S. L. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp364 · Cited by 81 · see citing works
Genetics of autoimmune diseases: perspectives from genome-wide association studies
Kochi, Y. (2016) · International Immunology · doi:10.1093/intimm/dxw002 · Cited by 73 · see citing works
Genetic Regulation of Serum Cytokines in Systemic Lupus Erythematosus
Kariuki, S. N., & Niewold, T. (2009) · Translational Research: The Journal of Laboratory and Clinical Medicine · doi:10.1016/j.trsl.2009.08.012 · Cited by 72 · see citing works
Mass spectrometry-based plasma proteomics: state of the art and future outlook
Pernemalm, M., & Lehtiö, J. (2014) · Expert Review of Proteomics · doi:10.1586/14789450.2014.901157 · Cited by 65 · see citing works
ImmVar project: Insights and design considerations for future studies of “healthy” immune variation
Jager, P. L. D., Hacohen, N., Mathis, D. J., Regev, A., Stranger, B. E., & Benoist, C. O. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2015.03.003 · Cited by 61 · see citing works
Novel Gene Variants Predict Serum Levels of the Cytokines IL-18 and IL-1ra in Older Adults
Matteini, A., Li, J., Lange, E., Tanaka, T., Lange, L., Tracy, R., Wang, Y., Biggs, M., Arking, D., Fallin, M., et al. (2013) · Cytokine · doi:10.1016/j.cyto.2013.10.002 · Cited by 59 · see citing works
The habitual, diverse and surmountable obstacles to human immunology research
Hayday, A., & Peakman, M. (2008) · Nature Immunology · doi:10.1038/ni0608-575 · Cited by 58 · see citing works
Seasonal changes in gene expression represent cell-type composition in whole blood
de Jong, S., Neeleman, M., Luykx, J. J., ten Berg, M. J., Strengman, E., Breeijen, H. H. D., Stijvers, L. C., Buizer‐Voskamp, J. E., Bakker, S. C., Kahn, R. S., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt665 · Cited by 40 · see citing works
Chattopadhyay, P. K., & Roederer, M. (2015) · American Journal of Transplantation · doi:10.1111/ajt.13193 · Cited by 37 · see citing works
The use of multiplex platforms for absolute and relative protein quantification of clinical material
Christiansson, L., Mustjoki, S., Simonsson, B., Olsson-Strömberg, U., Loskog, A. S. I., & Mangsbo, S. M. (2014) · EuPA Open Proteomics · doi:10.1016/j.euprot.2014.02.002 · Cited by 34 · see citing works
The human condition: an immunological perspective
Germain, R. N., & Schwartzberg, P. L. (2011) · Nature Immunology · doi:10.1038/ni0511-369 · Cited by 24 · see citing works
Systems vaccinology: a promise for the young and the poor
Amenyogbe, N., Levy, O., & Kollmann, T. R. (2015) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2014.0340 · Cited by 23 · see citing works
Powerful Populations Respond to Viruses and Vaccines
Brodin, P. (2015) · Immunity · doi:10.1016/j.immuni.2015.11.018 · Cited by 2 · see citing works
Self-citationDRUG-INDUCED mRNA SIGNATURES ARE ENRICHED FOR THE MINORITY OF GENES THAT ARE HIGHLY HERITABLE
GAO, T., Brodin, P., Davis, M. M., et al. (2014) · Pacific Symposium on Biocomputing (PSB) · doi:10.1142/9789814644730_0038 · Cited by 1 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Single-cell eQTL mapping identifies cell type–specific genetic control of autoimmune disease
Yazar, S., Alquicira-Hernandez, J., Wing, K., Senabouth, A., Gordon, M. G., Andersen, S., Lu, Q., Rowson, A., Taylor, T. R. P., Clarke, L., et al. (2022) · Science · doi:10.1126/science.abf3041 · Cited by 682 · see citing works
Immune function and micronutrient requirements change over the life course
Maggini, S., Pierre, A., & Calder, P. C. (2018) · Nutrients · doi:10.3390/nu10101531 · Cited by 710 · see citing works
A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring
Alpert, A., Pickman, Y., Leipold, M., Rosenberg-Hasson, Y., Ji, X., Gaujoux, R., Rabani, H., Starosvetsky, E., Kveler, K., Schaffert, S., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0381-y · Cited by 513 · see citing works
Self-citationSingle-cell chromatin modification profiling reveals increased epigenetic variations with aging
Cheung, P., Vallania, F., Warsinske, H. C., Donato, M., Schaffert, S., Chang, S. E., Dvorak, M., Dekker, C. L., Davis, M. M., Utz, P. J., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.079 · Cited by 323 · see citing works
“Recent publications have described increased variability in the immune systems of older versus younger human beings (Brodin and Davis, 2017; Kaczorowski et al., 2017).”
Self-citationUnderlying features of epigenetic aging clocks in vivo and in vitro.
Liu, Z., Leung, D., Thrush, K., Zhao, W., Ratliff, S., Tanaka, T., Schmitz, L. L., Smith, J. A., Ferrucci, L., & Levine, M. E. (2020) · Aging Cell · doi:10.1111/acel.13229 · Cited by 227 · see citing works
Organ-on-a-Chip for Cancer and Immune Organs Modeling
Sun, W., Luo, Z., Lee, J., Kim, H., Lee, K., Tebon, P., Feng, Y., Dokmeci, M. R., Sengupta, S., & Khademhosseini, A. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201801363 · Cited by 221 · see citing works
Preoperative stimulation of resolution and inflammation blockade eradicates micrometastases
Panigrahy, D., Gartung, A., Yang, J., Yang, H., Gilligan, M. M., Sulciner, M. L., Bhasin, S. S., Bielenberg, D. R., Chang, J., Schmidt, B. A., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci127282 · Cited by 132 · see citing works
Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy
Hartmann, F. J., Babdor, J., Gherardini, P. F., Amir, E.-A. D., Jones, K., Sahaf, B., Marquez, D. M., Krutzik, P., O’Donnell, E., Sigal, N., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.049 · Cited by 124 · see citing works
Current Challenges in Vaccinology
Kennedy, R. B., Ovsyannikova, I. G., Palese, P., & Poland, G. A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01181 · Cited by 113 · see citing works
Custovic, A., Belgrave, D., Lin, L., Bakhsoliani, E., Telcian, A. G., Solari, R., Murray, C. S., Walton, R. P., Curtin, J., Edwards, M. R., et al. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201708-1762oc · Cited by 95 · see citing works
Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer
Khan, Z., Di Nucci, F., Kwan, A., Hammer, C., Mariathasan, S., Rouilly, V., Carroll, J., Fontes, M., Ley Acosta, S., Guardino, E., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1922867117 · Cited by 91 · see citing works
ten Brink, T., Damanik, F., Rotmans, J. I., & Moroni, L. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202301939 · Cited by 71 · see citing works
3D Immunocompetent Organ‐on‐a‐Chip Models
Maharjan, S., Cecen, B., & Zhang, Y. S. (2020) · Small Methods · doi:10.1002/smtd.202000235 · Cited by 62 · see citing works
- Authors
- Brodin, P., & Davis, M. M.
- Affiliations
- Karolinska University Hospital (SE)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Brodin, Petter
- Venue
- Nature reviews. Immunology
- Published
- 2016-12-05
- Volume
- 17
- Issue
- 1
- Pages
- 21-29
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC5328245
- OpenAlex
- W2560758606
- Cited by
- 730
- References
- 107
- Citations by year
- 2026: 51 · 2025: 77 · 2024: 86 · 2023: 123 · 2022: 74 · 2021: 86 · 2020: 93 · 2019: 59 · 2018: 50 · 2017: 31
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Allergy and Infectious Diseases (U19AI090019, U19AI057229)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- systems immunology, microbiota, sex differences, immune cell composition, immune proteins, immune-mediated diseases, infectious disease risk
- MeSH terms
- Humans, Immune System
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