Adipose Tissue Inflammation Induces B Cell Inflammation and Decreases B Cell Function in Aging
Open accessAbstract
Aging is the greatest risk factor for developing chronic diseases. Inflamm-aging, the age-related increase in low-grade chronic inflammation, may be a common link in age-related diseases. This review summarizes recent published data on potential cellular and molecular mechanisms of the age-related increase in inflammation, and how these contribute to decreased humoral immune responses in aged mice and humans. Briefly, we cover how aging and related inflammation decrease antibody responses in mice and humans, and how obesity contributes to the mechanisms for aging through increased inflammation. We also report data in the literature showing adipose tissue infiltration with immune cells and how these cells are recruited and contribute to local and systemic inflammation. We show that several types of immune cells infiltrate the adipose tissue and these include macrophages, neutrophils, NK cells, innate lymphoid cells, eosinophils, T cells, B1, and B2 cells. Our main focus is how the adipose tissue affects immune responses, in particular B cell responses and antibody production. The role of leptin in generating inflammation and decreased B cell responses is also discussed. We report data published by us and by other groups showing that the adipose tissue generates pro-inflammatory B cell subsets which induce pro-inflammatory T cells, promote insulin resistance, and secrete pathogenic autoimmune antibodies.
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The number of B lymphocytes and macrophages in visceral adipose tissue from obese individuals is increased and correlated with BMI.
“The number of B lymphocytes and macrophages in visceral adipose tissue from obese individuals is also increased and is correlated with BMI55.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [55]
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Neutrophil Extracellular Traps Kill Bacteria
Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D. S., Weinrauch, Y., & Zychlinsky, A. (2004) · Science · doi:10.1126/science.1092385 · Cited by 10,268 · see citing works
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041 · see citing works
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199 · see citing works
Renehan, A. G., Tyson, M., Egger, M., Heller, R. F., & Zwahlen, M. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60269-x · Cited by 5,219 · see citing works
Inflammation and insulin resistance
Shoelson, S. E. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29069 · Cited by 4,769 · see citing works
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29881 · Cited by 4,664 · see citing works
Weight-Reducing Effects of the Plasma Protein Encoded by the <i>obese</i> Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451 · see citing works
Kim, H. J., Park, S. Y., Choi, Y. J., Han, S. J., Lee, K. W., & Kim, D. J. (2013) · Hormone Research in Paediatrics · doi:10.1159/000348848 · Cited by 3,061 · see citing works
Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity
Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W. Z., Strowig, T., Thaiss, C. A., Kau, A. L., Eisenbarth, S. C., Jurczak, M. J., et al. (2012) · Nature · doi:10.1038/nature10809 · Cited by 2,435 · see citing works
Subcutaneous and visceral adipose tissue: Structural and functional differences
Ibrahim, M. M. (2010) · Obesity Reviews · doi:10.1111/j.1467-789x.2009.00623.x · Cited by 2,238 · see citing works
Nishimura, S., Manabe, I., Nagasaki, M., Eto, K., Yamashita, H., Ohsugi, M., Otsu, M., Hara, K., Ueki, K., Sugiura, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.1964 · Cited by 2,230 · see citing works
Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis
Hakkim, A., Fürnrohr, B. G., Amann, K., Laube, B., Abed, U. A., Brinkmann, V., i, M. H., Voll, R. E., & Zychlinsky, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909927107 · Cited by 1,473 · see citing works
Normalization of obesity-associated insulin resistance through immunotherapy
Winer, S., Chan, Y., Paltser, G., Truong, D., Tsui, H., Bahrami, J., Dorfman, R., Wang, Y., Zielenski, J., Mastronardi, F., et al. (2009) · Nature Medicine · doi:10.1038/nm.2001 · Cited by 1,370 · see citing works
Leptin regulates proinflammatory immune responses
Loffreda, S., Yang, S., Lin, H., Karp, C. L., Brengman, M. L., Wang, D., Klein, A. S., Bulkley, G. B., Bao, C., Noble, P. W., et al. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.1.57 · Cited by 1,251 · see citing works
Systemic inflammation and disease progression in Alzheimer disease
Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., & Perry, V. H. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b6bb95 · Cited by 1,139 · see citing works
Fat tissue, aging, and cellular senescence
Tchkonia, T., Morbeck, D. E., Von Zglinicki, T., Van Deursen, J., Lustgarten, J., Scrable, H., Khosla, S., Jensen, M. D., & Kirkland, J. L. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00608.x · Cited by 1,094 · see citing works
Winer, D. A., Winer, S., Shen, L., Wadia, P. P., Yantha, J., Paltser, G., Tsui, H., Wu, P., Davidson, M. G., Alonso, M. N., et al. (2011) · Nature Medicine · doi:10.1038/nm.2353 · Cited by 1,050 · see citing works
Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase
Talukdar, S., Oh, D. Y., Bandyopadhyay, G. K., Li, D., Xu, J., McNelis, J., Lu, M. M., Li, P., Yan, Q., Zhu, Y., et al. (2012) · Nature Medicine · doi:10.1038/nm.2885 · Cited by 966 · see citing works
The weight of leptin in immunity
Cava, A. L., & Matarese, G. (2004) · Nature Reviews Immunology · doi:10.1038/nri1350 · Cited by 927 · cited 1× · see citing works
“Highserum levels of leptin contribute to the inflammatory state of the adipose tissue associated with obesity (87, 88).”
BackgroundRubtsov, A. V., Rubtsova, K., Fischer, A., Meehan, R. T., Gillis, J. Z., Kappler, J. W., & Marrack, P. (2011) · Blood · doi:10.1182/blood-2011-01-331462 · Cited by 808 · see citing works
The Origins and Drivers of Insulin Resistance
Johnson, A. M. F., & Olefsky, J. M. (2013) · Cell · doi:10.1016/j.cell.2013.01.041 · Cited by 639 · see citing works
A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice
Hao, Y., O'Neill, P., Naradikian, M. S., Scholz, J. L., & Cancro, M. P. (2011) · Blood · doi:10.1182/blood-2011-01-330530 · Cited by 622 · see citing works
Human Leptin Stimulates Proliferation and Activation of Human Circulating Monocytes
Santos‐Álvarez, J., Goberna, R., & Sánchez‐Margalet, V. (1999) · Cellular Immunology · doi:10.1006/cimm.1999.1490 · Cited by 600 · see citing works
Matarese, G., Moschos, S., & Mantzoros, C. S. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3137 · Cited by 559 · 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 · cited 1× · see citing works
“Defects in T cells (9–11), B cells (12, 13), and antigen-presenting cells (14, 15) have been reported and all contribute to the agerelated decrease in antibody production.”
BackgroundHuman Leptin Enhances Activation and Proliferation of Human Circulating T Lymphocytes
Martín-Romero, C., Santos‐Álvarez, J., Goberna, R., & Sánchez‐Margalet, V. (2000) · Cellular Immunology · doi:10.1006/cimm.1999.1594 · Cited by 524 · see citing works
DeFuria, J., Belkina, A. C., Jagannathan-Bogdan, M., Snyder-Cappione, J., Carr, J. D., Nersesova, Y. R., Markham, D., Strissel, K. J., Watkins, A. A., Zhu, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215840110 · Cited by 521 · see citing works
T-bet regulates IgG class switching and pathogenic autoantibody production
Peng, S. L., Szabo, S. J., & Glimcher, L. H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082114899 · Cited by 498 · see citing works
Obesity, Waist Circumference, Weight Change, and the Risk of Psoriasis in Women
Setty, A. R. (2007) · Archives of Internal Medicine · doi:10.1001/archinte.167.15.1670 · Cited by 485 · see citing works
Mundy, G. R. (2008) · Nutrition Reviews · doi:10.1111/j.1753-4887.2007.tb00353.x · Cited by 480 · see citing works
The Intestinal Immune System in Obesity and Insulin Resistance
Winer, D. A., Luck, H., Tsai, S. J., & Winer, S. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.01.003 · Cited by 476 · see citing works
Adipose tissue as an immunological organ
Grant, R. W., & Dixit, V. D. (2015) · Obesity · doi:10.1002/oby.21003 · Cited by 453 · see citing works
B‐cell diversity decreases in old age and is correlated with poor health status
Gibson, K. L., Wu, Y., Barnett, Y., Duggan, O., Vaughan, R., Kondeatis, E., Nilsson, B., Wikby, A., Kipling, D., & Dunn‐Walters, D. K. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2008.00443.x · Cited by 433 · see citing works
Smith, A. G., Sheridan, P. A., Harp, J. B., & Beck, M. A. (2007) · Journal of Nutrition · doi:10.1093/jn/137.5.1236 · Cited by 389 · see citing works
T cells and aging january 2002 update
Pawelec, G. (2002) · Frontiers in bioscience · doi:10.2741/a831 · Cited by 368 · see citing works
Age-Associated Defect in Human TLR-1/2 Function
van Duin, D., Mohanty, S., Thomas, V., Ginter, S., Montgomery, R. R., Fikrig, E., Allore, H. G., Medzhitov, R., & Shaw, A. C. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.2.970 · Cited by 352 · see citing works
Shulzhenko, N., Morgun, A., Hsiao, W., Battle, M., Yao, M., Gavrilova, O., Orandle, M., Mayer, L., Macpherson, A. J., McCoy, K. D., et al. (2011) · Nature Medicine · doi:10.1038/nm.2505 · Cited by 349 · see citing works
The network and the remodeling theories of aging: historical background and new perspectives
Franceschi, C., Valensin, S., Bonafè, M., Paolisso, G., Yashin, A. I., Monti, D., & De Benedictis, G. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00172-8 · Cited by 335 · see citing works
Frasca, D., Landin, A. M., Lechner, S. C., Ryan, J. G., Schwartz, R., Riley, R. L., & Blomberg, B. B. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.8.5283 · Cited by 333 · see citing works
Self-citationLee, B.-C., Kim, M., Pae, M., Yamamoto, Y., Eberlé, D., Shimada, T., Kamei, N., Park, H.-S., Sasorith, S., Woo, J. R., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.03.002 · Cited by 303 · see citing works
Unexpected trafficking of immune cells within the adipose tissue during the onset of obesity
Duffaut, C., Galitzky, J., Lafontan, M., & Bouloumié, A. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.05.002 · Cited by 296 · see citing works
Casas, R. M., Sacanella, E., & Estruch, R. (2014) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530314666140922153350 · Cited by 291 · see citing works
The burden of obesity on infectious disease
Karlsson, E. A., & Beck, M. A. (2010) · Experimental Biology and Medicine · doi:10.1258/ebm.2010.010227 · Cited by 290 · see citing works
Aging Up-Regulates Expression of Inflammatory Mediators in Mouse Adipose Tissue
Wu, D., Ren, Z., Pae, M., Guo, W., Cui, X., Merrill, A. H., & Meydani, S. N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.7.4829 · Cited by 288 · see citing works
The Impact of Obesity on Surgical Outcomes: A Review
CHOBANMDFACS, P., & FLANCBAUMMDFACS, L. (1997) · Journal of the American College of Surgeons · doi:10.1016/s1072-7515(97)00109-9 · Cited by 278 · see citing works
Haynes, L., Eaton, S. M., Burns, E. M., Randall, T. D., & Swain, S. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2433717100 · Cited by 270 · see citing works
Nishimoto, S., Fukuda, D., Higashikuni, Y., Tanaka, K., Hirata, Y., Murata, C., Kim‐Kaneyama, J., Sato, F., Bando, M., Yagi, S., et al. (2016) · Science Advances · doi:10.1126/sciadv.1501332 · Cited by 256 · see citing works
Effect of BMI and age on adipose tissue cellularity and differentiation capacity in women
van Harmelen, V., Skurk, T., Röhrig, K., Lee, Y.-M., Halbleib, M., Aprath-Husmann, I., & Hauner, H. (2003) · International Journal of Obesity · doi:10.1038/sj.ijo.0802314 · Cited by 249 · see citing works
E-proteins directly regulate expression of activation-induced deaminase in mature B cells
Sayegh, C. E., Quong, M. W., Agata, Y., & Murre, C. (2003) · Nature Immunology · doi:10.1038/ni923 · Cited by 246 · see citing works
The Obese Surgical Patient: A Susceptible Host for Infection
Anaya, D. A., & Dellinger, E. P. (2006) · Surgical Infections · doi:10.1089/sur.2006.7.473 · Cited by 241 · see citing works
Naradikian, M. S., Myles, A., Beiting, D. P., Roberts, K. J., Dawson, L. A., Herati, R. S., Bengsch, B., Linderman, S. L., Stelekati, E., Spolski, R. J., et al. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600522 · Cited by 239 · see citing works
Diet-Induced Obesity Impairs the T Cell Memory Response to Influenza Virus Infection
Karlsson, E. A., Sheridan, P. A., & Beck, M. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903220 · Cited by 236 · see citing works
Agrawal, S., Gollapudi, S. V. S., Su, H., & Gupta, S. (2011) · Journal of Clinical Immunology · doi:10.1007/s10875-010-9507-1 · Cited by 232 · see citing works
Obesity decreases <scp>B</scp> cell responses in young and elderly individuals
Frasca, D., Ferracci, F., Diaz, A., Romero, M., Lechner, S., & Blomberg, B. B. (2016) · Obesity · doi:10.1002/oby.21383 · Cited by 228 · see citing works
Self-citationInverse association between adiposity and telomere length: The fels longitudinal study
Lee, M., Martin, H. B., Firpo, M. A., & Demerath, E. W. (2010) · American Journal of Human Biology · doi:10.1002/ajhb.21109 · Cited by 213 · see citing works
The Impact of Increased Body Mass Index on the Clinical Course of Crohn’s Disease
Hass, D. J., Brensinger, C. M., Lewis, J. D., & Lichtenstein, G. R. (2006) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2005.12.015 · Cited by 213 · see citing works
Reduced tetanus antibody titers in overweight children
Eliakim, A., Swindt, C., Zaldivar, F., Casali, P., & Cooper, D. M. (2006) · Autoimmunity · doi:10.1080/08916930600597326 · Cited by 209 · see citing works
Role of CMV in immune senescence.
Pawelec, G., & Derhovanessian, E. (2011) · Virus Research · doi:10.1016/j.virusres.2010.09.010 · Cited by 201 · see citing works
Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity
Boulenouar, S., Michelet, X., Duquette, D., Álvarez, D., Hogan, A. E., Dold, C., O’Connor, D. B., Stutte, S., Tavakkoli, A., Winters, D., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.01.008 · Cited by 192 · see citing works
In senescence, age‐associated B cells secrete TNF α and inhibit survival of B‐cell precursors*
Ratliff, M., Alter, S., Frasca, D., Blomberg, B. B., & Riley, R. L. (2013) · Aging Cell · doi:10.1111/acel.12055 · Cited by 183 · see citing works
Self-citationState of the union between metabolism and the immune system in type 2 diabetes
Nikolajczyk, B. S., Jagannathan‐Bogdan, M., Shin, H., & Gyurko, R. (2011) · Genes and Immunity · doi:10.1038/gene.2011.14 · Cited by 165 · see citing works
Age‐associated B cells: key mediators of both protective and autoreactive humoral responses
Naradikian, M. S., Hao, Y., & Cancro, M. P. (2015) · Immunological Reviews · doi:10.1111/imr.12380 · Cited by 152 · see citing works
Frasca, D., Van der Put, E., Riley, R. L., & Blomberg, B. B. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.4.2155 · Cited by 150 · see citing works
Self-citationB Lymphocytes in obesity-related adipose tissue inflammation and insulin resistance
Winer, D. A., Winer, S., Chng, M. H. Y., Shen, L., & Engleman, E. G. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1486-y · Cited by 144 · see citing works
Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humans
Frasca, D., Diaz, A., Romero, M., Landin, A. M., Phillips, M., Lechner, S. C., Ryan, J. G., & Blomberg, B. B. (2010) · Vaccine · doi:10.1016/j.vaccine.2010.10.023 · Cited by 143 · see citing works
Self-citationSystematic review: adipose tissue, obesity and gastrointestinal diseases
John, B. J., Irukulla, S., Abulafi, A. M., Kumar, D., & Mendall, M. A. (2006) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2006.02915.x · Cited by 128 · see citing works
Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling
Ying, W., Wollam, J., Ofrecio, J. M., Bandyopadhyay, G., El Ouarrat, D., Lee, Y. S., Oh, D. Y., Li, P., Osborn, O., & Olefsky, J. M. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90350 · Cited by 128 · cited 1× · see citing works
“B2 cells may also be recruited to the AT through leukotriene LTB4/ LTB4R1 signaling (62).”
BackgroundCytomegalovirus (CMV) seropositivity decreases B cell responses to the influenza vaccine
Frasca, D., Diaz, A., Romero, M., Landin, A. M., & Blomberg, B. B. (2015) · Vaccine · doi:10.1016/j.vaccine.2015.01.071 · Cited by 116 · see citing works
Self-citationHigh TNF-α levels in resting B cells negatively correlate with their response
Frasca, D., Diaz, A., Romero, M., Landin, A. M., & Blomberg, B. B. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.004 · Cited by 115 · see citing works
Self-citationImpaired Wound Healing Predisposes Obese Mice to Severe Influenza Virus Infection
O’Brien, K., Vogel, P., Duan, S., Govorkova, E. A., Webby, R. J., McCullers, J. A., & Schultz‐Cherry, S. (2011) · The Journal of Infectious Diseases · doi:10.1093/infdis/jir729 · Cited by 113 · see citing works
Duggal, N. A., Upton, J., Phillips, A. C., Sapey, E., & Lord, J. (2013) · Aging Cell · doi:10.1111/acel.12114 · Cited by 110 · see citing works
Adipose tissue, diet and aging
Zamboni, M. M., Rossi, A. P., Fantin, F., Zamboni, G. A., Chirumbolo, S., Zoico, E., & Mazzali, G. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.11.008 · Cited by 110 · see citing works
Inflammation in subcutaneous adipose tissue: relationship to adipose cell size
McLaughlin, T., Deng, A., Yee, G., Lamendola, C., Reaven, G., Tsao, P. S., Cushman, S. W., & Sherman, A. (2010) · Diabetologia · doi:10.1007/s00125-009-1496-3 · Cited by 105 · see citing works
Yang, Y., Chen, M., Clements, R. H., Abrams, G. A., Aprahamian, C. J., & Harmon, C. M. (2008) · Cellular Physiology and Biochemistry · doi:10.1159/000185527 · Cited by 100 · see citing works
A Molecular Mechanism for TNF-α–Mediated Downregulation of B Cell Responses
Frasca, D., Romero, M., Diaz, A., Alter-Wolf, S., Ratliff, M., Landin, A. M., Riley, R. L., & Blomberg, B. B. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003964 · Cited by 98 · see citing works
Self-citationAssociation between LTA, TNF and AGER Polymorphisms and Late Diabetic Complications
Lindholm, E., Bakhtadze, E., Cilio, C., Agardh, E., Groop, L., & Agardh, C. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002546 · Cited by 92 · see citing works
Unique biomarkers for B-cell function predict the serum response to pandemic H1N1 influenza vaccine
Frasca, D., Diaz, A., Romero, M., Phillips, M., Mendez, N. V., Landin, A. M., & Blomberg, B. B. (2012) · International Immunology · doi:10.1093/intimm/dxr123 · Cited by 86 · see citing works
Self-citationKhurana, S., Frasca, D., Blomberg, B., & Golding, H. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002920 · Cited by 85 · see citing works
Self-citationObesity induces pro-inflammatory B cells and impairs B cell function in old mice
Frasca, D., Diaz, A., Romero, M., Vazquez, T., & Blomberg, B. B. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.01.004 · Cited by 80 · see citing works
Self-citationMilner, J. J., Sheridan, P. A., Karlsson, E. A., Schultz‐Cherry, S., Shi, Q., & Beck, M. A. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202429 · Cited by 78 · see citing works
Nucleic Acid-Targeting Pathways Promote Inflammation in Obesity-Related Insulin Resistance
Revelo, X. S., Ghazarian, M., Chng, M. H. Y., Luck, H., Kim, J. H., Zeng, K., Shi, S. Y., Tsai, S. J., Lei, H., Kenkel, J. A., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.024 · Cited by 78 · see citing works
Frasca, D., Diaz, A., Romero, M., Mendez, N. V., Landin, A. M., & Blomberg, B. B. (2013) · Immunity & Ageing · doi:10.1186/1742-4933-10-14 · Cited by 77 · see citing works
Self-citationO'Shea, D. B., Corrigan, M., Dunne, M. R., Jackson, R. W., Woods, C. P., Gaoatswe, G., Moynagh, P. N., O’Connell, J., & Hogan, A. E. (2013) · International Journal of Obesity · doi:10.1038/ijo.2013.16 · Cited by 77 · see citing works
Wu, L., Parekh, V. V., Hsiao, J., Kitamura, D., & Kaer, L. V. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1324052111 · Cited by 70 · see citing works
Tumor necrosis factor-a, biologic agents and cardiovascular risk
Sarzi‐Puttini, P., Atzeni, F., Doria, A., Iaccarino, L., & Turiel, M. (2005) · Lupus · doi:10.1191/0961203305lu2220oa · Cited by 69 · see citing works
MicroRNAs miR-155 and miR-16 decrease AID and E47 in B cells from elderly individuals
Frasca, D., Diaz, A., Romero, M., Ferracci, F., & Blomberg, B. B. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500520 · Cited by 69 · see citing works
Self-citationHoward, W. A., Gibson, K. L., & Dunn‐Walters, D. K. (2006) · Rejuvenation Research · doi:10.1089/rej.2006.9.117 · Cited by 68 · see citing works
Hukshorn, C. J., & Saris, W. H. M. (2004) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200411000-00007 · Cited by 65 · see citing works
Boraschi, D., Giudice, G. D., Dutel, C., Ivanoff, B., Rappuoli, R., & Grubeck‐Loebenstein, B. (2010) · Vaccine · doi:10.1016/j.vaccine.2010.03.035 · Cited by 64 · see citing works
Ovsyannikova, I. G., White, S. J., Larrabee, B. R., Grill, D. E., Jacobson, R. M., & Poland, G. A. (2013) · Vaccine · doi:10.1016/j.vaccine.2013.12.009 · Cited by 56 · see citing works
Hepatitis B vaccine response in obesity: A meta-analysis
Fan, W., Chen, X., Shen, C., Guo, Z., & Dong, C. (2016) · Vaccine · doi:10.1016/j.vaccine.2016.08.027 · Cited by 55 · see citing works
van Dijk‐Härd, I., Söderström, I., Feld, S., Holmberg, D., & Lundkvist, I. (1997) · European Journal of Immunology · doi:10.1002/eji.1830270613 · Cited by 50 · see citing works
B cells as under-appreciated mediators of non-autoimmune inflammatory disease
Nikolajczyk, B. (2010) · Cytokine · doi:10.1016/j.cyto.2010.02.022 · Cited by 45 · 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
Isaacs, J. D. (2009) · Expert Opinion on Biological Therapy · doi:10.1517/14712590903379494 · Cited by 41 · see citing works
Memory B cells form in aged mice despite impaired affinity maturation and germinal center kinetics
Goenka, R., Scholz, J. L., Naradikian, M. S., & Cancro, M. P. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2013.12.013 · Cited by 38 · see citing works
Innate lymphoid cells as novel regulators of obesity and its‐associated metabolic dysfunction
Yang, D., Yang, W., Tian, Z., van Velkinburgh, J. C., Song, J. J., Wu, Y., & Ni, B. (2016) · Obesity Reviews · doi:10.1111/obr.12397 · Cited by 14 · see citing works
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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty
Ferrucci, L., & Fabbri, E. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0064-2 · Cited by 3,690 · see citing works
Cancro, M. P. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-092419-031130 · Cited by 464 · see citing works
Livshits, G., & Kalinkovich, A. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100980 · Cited by 239 · see citing works
Camell, C. D., Günther, P. S., Lee, A., Goldberg, E. L., Spadaro, O., Youm, Y., Bartke, A., Hubbard, G. B., Ikeno, Y., Ruddle, N. H., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.10.006 · Cited by 215 · see citing works
The Role of the Adipokine Leptin in Immune Cell Function in Health and Disease
Kiernan, K., & MacIver, N. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.622468 · Cited by 201 · see citing works
Han, Z., Wang, K., Ding, S., & Zhang, M. (2024) · Bone Research · doi:10.1038/s41413-024-00375-z · Cited by 189 · see citing works
Emerging mechanisms of obesity-associated immune dysfunction
Shaikh, S. R., Beck, M. A., Alwarawrah, Y., & MacIver, N. J. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00932-2 · Cited by 173 · see citing works
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Trim, W. V., Turner, J. E., & Thompson, D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00169 · Cited by 167 · see citing works
Immune and non-immune functions of adipose tissue leukocytes
Trim, W. V., & Lynch, L. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00635-7 · Cited by 147 · see citing works
Gkrinia, E. M. M., & Belančić, A. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47050357 · Cited by 129 · see citing works
Immune aging in diabetes and its implications in wound healing
Moura, J., Madureira, P., Leal, E. C., Fonseca, A. C., & Carvalho, E. (2019) · Clinical Immunology · doi:10.1016/j.clim.2019.02.002 · Cited by 116 · see citing works
Obesity and its impact on COVID-19
de Leeuw, A. J. M., Luttikhuis, M. A. M. O., Wellen, A. C., Müller, C., & Calkhoven, C. F. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-021-02072-4 · Cited by 103 · see citing works
Komakula, S. S. B., Tůmová, J., Kumaraswamy, D., Burchat, N., Vartanian, V. L., Ye, H., Dobrzyń, A., Lloyd, R. S., & Sampath, H. (2018) · Scientific Reports · doi:10.1038/s41598-018-33151-1 · Cited by 80 · see citing works
Sex‐associated differences between BMI and SARS‐CoV‐2 antibody titers following the BNT162b2 vaccine
Yamamoto, S., Mizoue, T., Tanaka, A., Oshiro, Y., Inamura, N., Konishi, M., Ozeki, M., Miyo, K., Sugiura, W., Sugiyama, H., et al. (2022) · Obesity · doi:10.1002/oby.23417 · Cited by 62 · see citing works
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Couturier, J. P., & Lewis, D. E. (2018) · Current HIV/AIDS Reports · doi:10.1007/s11904-018-0378-z · Cited by 61 · see citing works
Srivastava, A., Yadav, T. C., Khera, H. K., Mishra, P., Raghuwanshi, N., Pruthi, V., & Prasad, R. (2021) · Journal of Autoimmunity · doi:10.1016/j.jaut.2021.102614 · Cited by 53 · see citing works
Ryu, J. Y., Choi, H. M., Yang, H.-I., & Kim, K. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186887 · Cited by 51 · see citing works
Evidences from Clinical Trials in Down Syndrome: Diet, Exercise and Body Composition
Martínez‐Espinosa, R. M., Vila, M. D. M., & García-Galbis, M. R. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17124294 · Cited by 50 · see citing works
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Lee, K.-A., Robbins, P. D., & Camell, C. D. (2021) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2021.01.003 · Cited by 47 · see citing works
Merino, K. M., Allers, C., Didier, E. S., & Kuroda, M. J. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01693 · Cited by 41 · see citing works
Trim, W. V., Walhin, J., Koumanov, F., Bouloumié, A., Lindsay, M. A., Chen, Y., Travers, R. L., Turner, J. E., & Thompson, D. (2021) · The Journal of Physiology · doi:10.1113/jp280977 · Cited by 39 · see citing works
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Shaikh, S. R., MacIver, N. J., & Beck, M. A. (2022) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-062320-115937 · Cited by 27 · see citing works
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Vinaik, R., Barayan, D., & Jeschke, M. G. (2020) · Endocrinology · doi:10.1210/endocr/bqaa116 · Cited by 23 · see citing works
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Yuan, Q., Chen, H., Li, X., & Wei, J. (2019) · Clinical Rheumatology · doi:10.1007/s10067-019-04831-8 · Cited by 15 · see citing works
Daley, A. D., & Bénézech, C. (2024) · Immunological Reviews · doi:10.1111/imr.13339 · Cited by 16 · see citing works
Zukeran, M. S., Ritti-Dias, R., Franco, F. G., Cendoroglo, M., de Matos, L. N., & Ribeiro, S. M. L. (2018) · The Journal of Nutrition, Health & Aging · doi:10.1007/s12603-018-1128-z · Cited by 15 · see citing works
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Gasmi, A., Chirumbolo, S., Peana, M., Mujawdiya, P. K., Dadar, M., Menzel, A., & Bjørklund, G. (2020) · Current Medicinal Chemistry · doi:10.2174/0929867327999200917150652 · Cited by 14 · see citing works
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Dai, W., Liu, X., Su, H., Li, X., Xu, Y., & Yu, Y. (2022) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2022.04.008 · Cited by 10 · see citing works
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Geitgey, D. K., Lee, M., Cottrill, K. A., Jaffe, M., Pilcher, W., Bhasin, S. S., Randall, J. M., Ross, A. J., Salemi, M., Castillo‐Castrejón, M., et al. (2023) · JNCI Monographs · doi:10.1093/jncimonographs/lgad014 · Cited by 9 · see citing works
Toll-like receptors in B cells and obesity
Wang, P., Hou, C., Wong, F. S., & Li, W. (2025) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2025.05.005 · Cited by 8 · see citing works
Yamaguchi, K., Fukushima, Y., Yamaguchi, A., Itai, M., Shin, Y., Uno, S., Muto, S., Kouno, S., Tsurumaki, H., Yatomi, M., et al. (2022) · Respiratory Medicine · doi:10.1016/j.rmed.2022.106741 · Cited by 8 · see citing works
Adipose immune microenvironment: catalyst of age-related adipose tissue dysfunction
Song, Y., Xing, H., Luo, Y., Li, B., Li, Y., & Dong, Z. (2025) · Immunity & Ageing · doi:10.1186/s12979-025-00545-5 · Cited by 8 · see citing works
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Lemus‐Conejo, A., Medrano, M., López, S., Millán-Linares, M. C., Rosillo, M. Á., Pérez‐Simón, J. A., Muriana, F. J. G., & Abia, R. (2021) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202001203 · Cited by 7 · see citing works
Respiratory diseases and obesity: special phenotype or independent events: Review
Shchepikhin, E. I., Shmelev, E. I., & Сергеевна, З. А. (2022) · Terapevticheskii arkhiv · doi:10.26442/00403660.2022.03.201412 · Cited by 8 · see citing works
Impact of Metabolic States on SARS-CoV-2 Vaccine Responses in Mouse Models of Obesity and Diabetes
Smith, O. A., Fujimoto, B., Wong, T. A. S., To, A., Odo, T., Ball, A. H., Haun, B. K., Muramatsu, H., Tam, Y. K., Pardi, N., et al. (2024) · COVID · doi:10.3390/covid5010002 · Cited by 6 · see citing works
Hidayat, R., Mustika, A. P., Avisha, F., Djuliannisaa, Z., Winari, D. D., Putri, R. A., Lisman, H. M., Davin, V., Fathi, G. C., Widhani, A., et al. (2022) · Acta Medica Academica · doi:10.5644/ama2006-124.374 · Cited by 5 · see citing works
Szczerbiński, Ł., Okruszko, M. A., Szabłowski, M., Warpechowski, J. J., Paszko, A., Citko, A., Konopka, P., Bauer, W., & Kretowski, A. J. (2023) · Vaccines · doi:10.3390/vaccines11010149 · Cited by 5 · see citing works
Hammad, N., Kadry, H. M., Malek, M. M., Bahgat, S. M., Abdelsalam, N. M., Afifi, A. H. M., & Abo-Alella, D. (2022) · Vaccines · doi:10.3390/vaccines10101706 · Cited by 4 · see citing works
Hoang, D. V., Yamamoto, S., Fukunaga, A., Inoue, Y., Mizoue, T., & Ohmagari, N. (2022) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-022-00918-6 · Cited by 4 · see citing works
The Immune System and Inflammation in Type 2 Diabetes
García-Macedo, R., & Fortis, M. D. L. Á. (2023) · Springer eBooks · doi:10.1007/978-3-031-25519-9_12 · Cited by 5 · see citing works
Function and Regulation of Age‐Associated B Cells in Diseases
Geng, Z., Cao, Y., Zhao, L., Wang, L., Dong, Y., Bi, Y., & Liu, G. (2025) · Journal of Cellular Physiology · doi:10.1002/jcp.31522 · Cited by 3 · see citing works
Age-Dependent Effect of Calcitriol on Mouse Regulatory T and B Lymphocytes
Śnieżewska, A., Anisiewicz, A., Gdesz-Birula, K., Wietrzyk, J., & Filip‐Psurska, B. (2023) · Nutrients · doi:10.3390/nu16010049 · Cited by 3 · see citing works
Characteristics and mechanisms of subcutaneous and visceral adipose tissue aging
Xu, P., Wang, Y., & Liu, K. (2024) · Chinese Journal of Plastic and Reconstructive Surgery · doi:10.1016/j.cjprs.2024.04.001 · Cited by 3 · see citing works
Ye, X.-R., Shi, D.-Q., Li, R. L., Li, Y., Zhang, L., Shi, L., & Xiao, Y. (2026) · Experimental Gerontology · doi:10.1016/j.exger.2026.113044 · Cited by 2 · see citing works
Aging induces Nlrp3 inflammasome dependent adipose B cell expansion to impair metabolic homeostasisPreprint
Camell, C. D., Lee, A., Günther, P. S., Goldberg, E. L., Spadaro, O., Youm, Y., Bartke, A., Hubbard, G. B., Ikeno, Y., Ruddle, N. H., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/607192 · Cited by 2 · see citing works
Unraveling the syndrome of age-associated diseases: Common pathways and novel therapeutic strategies
Mertelsmann, R. H., Faletti, L. E., & Zirlik, K. (2019) · Journal of Science Humanities and Arts - JOSHA · doi:10.17160/josha.6.2.539 · Cited by 1 · see citing works
Pawelec, G., & Müller, L. (2024) · Springer eBooks · doi:10.1007/978-3-030-74720-6_104 · Cited by 1 · see citing works
Inflammation and Its Role in Obesity-Related Complications
Singh, M. M., Sharma, J. R., Agraval, H., & Yadav, U. C. S. (2020) · Springer eBooks · doi:10.1007/978-3-030-53370-0_10
Investigating the Role of Insulin Receptor Signaling in B Lymphocyte Function
Chan, Y. T. (2019) · TSpace (University of Toronto)
Pawelec, G., & Müller, L. (2021) · Springer eBooks · doi:10.1007/978-3-030-01782-8_104-1
Ratnawati, H., Tih, F., Puspasari, G., Pelapelapon, A. A., & Felim, S. (2025) · Exploration of Immunology · doi:10.37349/ei.2025.1003180
Hoang, D. V., Yamamoto, S., Fukunaga, A., Inoue, Y., Mizoue, T., & Ohmagari, N. (2022) · Figshare · doi:10.6084/m9.figshare.21332680
Westbury, B. J., Williams, E. J., Berthon, B. S., Williams, L. M., Scott, H. A., Brown, A. M., Horvat, J. C., & Wood, L. G. (2026) · Proceedings of The Nutrition Society · doi:10.1017/s0029665126103176
- Authors
- Frasca, D., & Blomberg, B. B.
- Affiliations
- University of Miami (US)
- Corresponding author
- Blomberg, Bonnie B.
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2017-08-28
- Volume
- 8
- Pages
- 1003-1003
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC5581329
- OpenAlex
- W2747063627
- Cited by
- 66
- References
- 97
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 14 · 2021: 9 · 2020: 8 · 2019: 8 · 2018: 6 · 2017: 1
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (AG023717, AG32576, AI096446, AG042826, AG032576)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- inflammaging, adipose tissue inflammation, B cell function, aging, obesity, humoral immune response, antibody production, immune cell infiltration, adipose tissue macrophages, leptin, insulin resistance, autoantibodies, T cell polarization
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