{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:39:40Z","timestamp":1793234380019,"version":"4.5.0"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Advanced chronic kidney disease (CKD) is associated with impaired humoral immunity, contributing to increased infection-related mortality and suboptimal vaccine responses, as notably observed during the COVID-19 pandemic. CKD is also marked by the accumulation of uremic toxins, but whether they directly influence T and B cell functionality remains unclear. In this translational study, we integrated clinical and biological data from 106 CKD patients with mechanistic insights from in vitro and in vivo murine models to identify the mechanisms underlying CKD-associated defects in humoral responses against T cell-dependent antigens. Contrary to our initial hypothesis, indoxyl sulfate\u2014despite its known ability to activate Aryl hydrocarbon Receptor signaling in monocytes\u2014did not directly impair T\u2013B cell cooperation in coculture assays. Similarly, plasma levels of ten major uremic toxins showed no correlations with vaccine-induced antibody titers in patients. Instead, systemic inflammation emerged as the primary driver of defective humoral immunity. Murine models further confirmed that inflammation, rather than uremia alone, induces lymphopenia, disrupts lymphoid architecture, and ultimately impairs antibody production. These findings indicate that CKD-associated inflammation, rather than a direct effect of uremic toxins on adaptive immune effectors, underlies humoral immune dysfunction in CKD. Targeting inflammation may, therefore, offer a promising strategy to improve vaccine efficacy and reduce infection-related complications in this vulnerable population.<\/jats:p>","DOI":"10.3390\/toxins18020104","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T15:57:29Z","timestamp":1771516649000},"page":"104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Chronic Kidney Disease-Associated Defect in Humoral Immune Response Is Driven by Inflammation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1000-4737","authenticated-orcid":false,"given":"Maxime","family":"Espi","sequence":"first","affiliation":[{"name":"CIRI-Centre Int\u00e9gratif de Recherche en Immunologie, INSERM U1111, Universit\u00e9 Claude Bernard Lyon I, CNRS UMR 5308, Ecole Normale Sup\u00e9rieure de Lyon, Universit\u00e9 de Lyon, 69007 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon I, 69100 Villeurbanne, France"},{"name":"Department of Nephrology, Dialysis and Clinical Nutrition, Hospices Civils de Lyon, Hopital Lyon Sud, Oullins-Pierre B\u00e9nite, 69495 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2162-5873","authenticated-orcid":false,"given":"Xavier","family":"Charmetant","sequence":"additional","affiliation":[{"name":"CIRI-Centre Int\u00e9gratif de Recherche en Immunologie, INSERM U1111, Universit\u00e9 Claude Bernard Lyon I, CNRS UMR 5308, Ecole Normale Sup\u00e9rieure de Lyon, Universit\u00e9 de Lyon, 69007 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon I, 69100 Villeurbanne, France"},{"name":"Department of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon, Edouard Herriot Hospital, 69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floriane","family":"Fusil","sequence":"additional","affiliation":[{"name":"CIRI-Centre Int\u00e9gratif de Recherche en Immunologie, INSERM U1111, Universit\u00e9 Claude Bernard Lyon I, CNRS UMR 5308, Ecole Normale Sup\u00e9rieure de Lyon, Universit\u00e9 de Lyon, 69007 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6682-2029","authenticated-orcid":false,"given":"Cyrille","family":"Mathieu","sequence":"additional","affiliation":[{"name":"CIRI-Centre Int\u00e9gratif de Recherche en Immunologie, INSERM U1111, Universit\u00e9 Claude Bernard Lyon I, CNRS UMR 5308, Ecole Normale Sup\u00e9rieure de Lyon, Universit\u00e9 de Lyon, 69007 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9233-9161","authenticated-orcid":false,"given":"Marie","family":"Legras","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hypertension and Dialysis, Hospices Civils de Lyon, Edouard Herriot Hospital, 69003 Lyon, France"},{"name":"CarMeN, INSERM U1060, INRA U1397, Universit\u00e9 Claude Bernard Lyon 1, Oullins-Pierre B\u00e9nite, 69310 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2092-9979","authenticated-orcid":false,"given":"Caroline","family":"Pelletier","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hypertension and Dialysis, Hospices Civils de Lyon, Edouard Herriot Hospital, 69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7641-4707","authenticated-orcid":false,"given":"Griet","family":"Glorieux","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Pediatrics, Nephrology Unit, Ghent University Hospital, 90000 Gent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Soulage","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon I, 69100 Villeurbanne, France"},{"name":"CarMeN, INSERM U1060, INRA U1397, Universit\u00e9 Claude Bernard Lyon 1, Oullins-Pierre B\u00e9nite, 69310 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5076-2420","authenticated-orcid":false,"given":"Laetitia","family":"Koppe","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon I, 69100 Villeurbanne, France"},{"name":"Department of Nephrology, Dialysis and Clinical Nutrition, Hospices Civils de Lyon, Hopital Lyon Sud, Oullins-Pierre B\u00e9nite, 69495 Lyon, France"},{"name":"CarMeN, INSERM U1060, INRA U1397, Universit\u00e9 Claude Bernard Lyon 1, Oullins-Pierre B\u00e9nite, 69310 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3648-8963","authenticated-orcid":false,"given":"Olivier","family":"Thaunat","sequence":"additional","affiliation":[{"name":"CIRI-Centre Int\u00e9gratif de Recherche en Immunologie, INSERM U1111, Universit\u00e9 Claude Bernard Lyon I, CNRS UMR 5308, Ecole Normale Sup\u00e9rieure de Lyon, Universit\u00e9 de Lyon, 69007 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon I, 69100 Villeurbanne, France"},{"name":"Department of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon, Edouard Herriot Hospital, 69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1016\/S0140-6736(25)01853-7","article-title":"Global, Regional, and National Burden of Chronic Kidney Disease in Adults, 1990\u20132023, and Its Attributable Risk Factors: A Systematic Analysis for the Global Burden of Disease Study 2023","volume":"406","author":"Mark","year":"2025","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.kisu.2021.11.003","article-title":"Epidemiology of Chronic Kidney Disease: An Update 2022","volume":"12","author":"Kovesdy","year":"2022","journal-title":"Kidney Int. Suppl."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.kisu.2017.07.007","article-title":"Complications of Chronic Kidney Disease: Current State, Knowledge Gaps, and Strategy for Action","volume":"7","author":"Bello","year":"2017","journal-title":"Kidney Int. Suppl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1111\/j.1523-1755.2000.00337.x","article-title":"Mortality Caused by Sepsis in Patients with End-Stage Renal Disease Compared with the General Population","volume":"58","author":"Sarnak","year":"2000","journal-title":"Kidney Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41586-020-2521-4","article-title":"Factors Associated with COVID-19-Related Death Using OpenSAFELY","volume":"584","author":"Williamson","year":"2020","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.kint.2021.07.005","article-title":"The ROMANOV Study Found Impaired Humoral and Cellular Immune Responses to SARS-Cov-2 mRNA Vaccine in Virus Unexposed Patients Receiving Maintenance Hemodialysis","volume":"100","author":"Espi","year":"2021","journal-title":"Kidney Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.ekir.2023.01.004","article-title":"Rapid Waning of Immune Memory Against SARS-CoV-2 in Maintenance Hemodialysis Patients after mRNA Vaccination and Impact of a Booster Dose","volume":"8","author":"Espi","year":"2023","journal-title":"Kidney Int. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1492-7535.2005.01155.x","article-title":"Antibody Response to Engerix-B and Recombivax-HB Hepatitis B Vaccination in End-Stage Renal Disease","volume":"9","author":"Lacson","year":"2005","journal-title":"Hemodial. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.kint.2021.10.040","article-title":"A Prospective Observational Study for Justification, Safety, and Efficacy of a Third Dose of mRNA Vaccine in Patients Receiving Maintenance Hemodialysis","volume":"101","author":"Espi","year":"2022","journal-title":"Kidney Int."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Vanholder, R., Pletinck, A., Schepers, E., and Glorieux, G. (2018). Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update. Toxins, 10.","DOI":"10.3390\/toxins10010033"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Espi, M., Koppe, L., Fouque, D., and Thaunat, O. (2020). Chronic Kidney Disease-Associated Immune Dysfunctions: Impact of Protein-Bound Uremic Retention Solutes on Immune Cells. Toxins, 12.","DOI":"10.3390\/toxins12050300"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1681\/ASN.2007090971","article-title":"Impaired Immune Responses and Antigen-Specific Memory CD4+ T Cells in Hemodialysis Patients","volume":"19","author":"Litjens","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3109\/0886022X.2015.1106871","article-title":"Lymphocyte Depletion and Subset Alteration Correlate to Renal Function in Chronic Kidney Disease Patients","volume":"38","author":"Xiang","year":"2016","journal-title":"Ren. Fail."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.kint.2017.11.010","article-title":"Aryl Hydrocarbon Receptor Is Activated in Patients and Mice with Chronic Kidney Disease","volume":"93","author":"Dou","year":"2018","journal-title":"Kidney Int."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lano, G., Burtey, S., and Sall\u00e9e, M. (2020). Indoxyl Sulfate, a Uremic Endotheliotoxin. Toxins, 12.","DOI":"10.3390\/toxins12040229"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"116","DOI":"10.15252\/embj.201695027","article-title":"Aryl Hydrocarbon Receptor Is Required for Optimal B-Cell Proliferation","volume":"36","author":"Villa","year":"2017","journal-title":"EMBO J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.immuni.2017.12.012","article-title":"Regulation of the Immune Response by the Aryl Hydrocarbon Receptor","volume":"48","author":"Quintana","year":"2018","journal-title":"Immunity"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/ni.1915","article-title":"Activation of the Aryl Hydrocarbon Receptor Induces Human Type 1 Regulatory T Cell\u2013like and Foxp3+ Regulatory T Cells","volume":"11","author":"Gandhi","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"eabg1046","DOI":"10.1126\/scitranslmed.abg1046","article-title":"Inverted Direct Allorecognition Triggers Early Donor-Specific Antibody Responses after Transplantation","volume":"14","author":"Charmetant","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Charmetant, X., Rigault, G., Chen, C.-C., Kaminski, H., Visentin, J., Taton, B., Marseres, G., Mathias, V., Koenig, A., and Barba, T. (2025). \u03b3\u03b4 T Cells\u2019 Role in Donor-Specific Antibody Generation: Insights From Transplant Recipients and Experimental Models. Transpl. Int., 38.","DOI":"10.3389\/ti.2025.12859"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ndt\/17.suppl_8.16","article-title":"Immunological Basis of Inflammation in Dialysis","volume":"17","author":"Amore","year":"2002","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1111\/j.1523-1755.2005.00200.x","article-title":"IL-10, IL-6, and TNF-\u03b1: Central Factors in the Altered Cytokine Network of Uremia\u2014The Good, the Bad, and the Ugly","volume":"67","author":"Stenvinkel","year":"2005","journal-title":"Kidney Int."},{"key":"ref_23","first-page":"151","article-title":"Blood Serum Levels of IL-2, IL-6, IL-8, TNF-Alpha and IL-1beta in Patients on Maintenance Hemodialysis","volume":"3","author":"Rysz","year":"2006","journal-title":"Cell. Mol. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1159\/000534447","article-title":"Chronic Inflammation in Chronic Kidney Disease","volume":"148","author":"Yan","year":"2024","journal-title":"Nephron"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kadatane, S.P., Satariano, M., Massey, M., Mongan, K., and Raina, R. (2023). The Role of Inflammation in CKD. Cells, 12.","DOI":"10.3390\/cells12121581"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10844","DOI":"10.1096\/fj.201900730R","article-title":"Indoxyl Sulfate-Induced TNF-\u03b1 Is Regulated by Crosstalk between the Aryl Hydrocarbon Receptor, NF-\u03baB, and SOCS2 in Human Macrophages","volume":"33","author":"Kim","year":"2019","journal-title":"FASEB J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1161\/CIRCULATIONAHA.118.034588","article-title":"Uremic Toxin Indoxyl Sulfate Promotes Proinflammatory Macrophage Activation Via the Interplay of OATP2B1 and Dll4-Notch Signaling","volume":"139","author":"Nakano","year":"2019","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wakamatsu, T., Yamamoto, S., Ito, T., Sato, Y., Matsuo, K., Takahashi, Y., Kaneko, Y., Goto, S., Kazama, J.J., and Gejyo, F. (2018). Indoxyl Sulfate Promotes Macrophage IL-1\u03b2 Production by Activating Aryl Hydrocarbon Receptor\/NF-\u03ba\/MAPK Cascades, but the NLRP3 Inflammasome Was Not Activated. Toxins, 10.","DOI":"10.3390\/toxins10030124"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"RP87316","DOI":"10.7554\/eLife.87316","article-title":"Uremic Toxin Indoxyl Sulfate Induces Trained Immunity via the AhR-Dependent Arachidonic Acid Pathway in End-Stage Renal Disease (ESRD)","volume":"12","author":"Kim","year":"2024","journal-title":"eLife"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S76","DOI":"10.1046\/j.1523-1755.63.s84.14.x","article-title":"Uremia-Associated Immune Defect: The IL-10-CRP Axis","volume":"63","author":"Girndt","year":"2003","journal-title":"Kidney Int. Suppl."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"iii35","DOI":"10.1093\/ndt\/gfy175","article-title":"Chronic Inflammation in End-Stage Renal Disease and Dialysis","volume":"33","author":"Cobo","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"F1211","DOI":"10.1152\/ajprenal.00298.2018","article-title":"Chronic Kidney Disease and the Gut Microbiome","volume":"316","author":"Hobby","year":"2019","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/ki.2008.660","article-title":"Periodontal Disease Adversely Affects the Survival of Patients with End-Stage Renal Disease","volume":"75","author":"Kshirsagar","year":"2009","journal-title":"Kidney Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2215\/CJN.04610510","article-title":"Circulating Endotoxemia: A Novel Factor in Systemic Inflammation and Cardiovascular Disease in Chronic Kidney Disease","volume":"6","author":"McIntyre","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1053\/jren.2003.50021","article-title":"Inflammation in ESRD: Causes and Potential Consequences","volume":"13","author":"Kaysen","year":"2003","journal-title":"J. Ren. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s10047-018-1059-9","article-title":"The Biocompatibility and Bioactivity of Hemodialysis Membranes: Their Impact in End-Stage Renal Disease","volume":"22","author":"Amorim","year":"2019","journal-title":"J. Artif. Organs"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1038\/s41467-020-17135-2","article-title":"B Cell Zone Reticular Cell Microenvironments Shape CXCL13 Gradient Formation","volume":"11","author":"Cosgrove","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1038\/s41590-023-01503-3","article-title":"Conserved Stromal\u2013Immune Cell Circuits Secure B Cell Homeostasis and Function","volume":"24","author":"Stanossek","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1126\/science.aaa1300","article-title":"Inflammation-Induced Disruption of SCS Macrophages Impairs B Cell Responses to Secondary Infection","volume":"347","author":"Gaya","year":"2015","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/nri3552","article-title":"Sepsis-Induced Immunosuppression: From Cellular Dysfunctions to Immunotherapy","volume":"13","author":"Hotchkiss","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1038\/s41467-025-57706-9","article-title":"PD-L1+ Plasma Cells Suppress T Lymphocyte Responses in Patients with Sepsis and Mouse Sepsis Models","volume":"16","author":"Gossez","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Schrijver, I.T., Th\u00e9roude, C., and Roger, T. (2019). Myeloid-Derived Suppressor Cells in Sepsis. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00327"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1097\/CCM.0b013e3181e78ad0","article-title":"Role of Regulatory T Cells in Long-Term Immune Dysfunction Associated with Severe Sepsis","volume":"38","author":"Nascimento","year":"2010","journal-title":"Crit. Care Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"He, P., Zhang, J., Tian, N., Deng, Y., Zhou, M., Tang, C., Ma, Y., and Zhang, M. (2025). The Relationship between C-Reactive Protein to Lymphocyte Ratio and the Prevalence of Chronic Kidney Disease in US Adults: A Cross-Sectional Study. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1469750"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1016\/j.kint.2016.12.015","article-title":"Expansion of Polymorphonuclear Myeloid-Derived Suppressor Cells in Patients with End-Stage Renal Disease May Lead to Infectious Complications","volume":"91","author":"Xing","year":"2017","journal-title":"Kidney Int."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Xing, Y.-F., Cai, J.-R., Qin, J.-J., Zhou, W.-Y., Li, C.-M., and Li, X. (2021). Expansion of Monocytic Myeloid-Derived Suppressor Cells in Patients Under Hemodialysis Might Lead to Cardiovascular and Cerebrovascular Events. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.577253"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1038\/s12276-025-01527-9","article-title":"Targeting Immunosenescence and Inflammaging: Advancing Longevity Research","volume":"57","author":"Nguyen","year":"2025","journal-title":"Exp. Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: A New Immune-Metabolic Viewpoint for Age-Related Diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1172\/JCI64098","article-title":"Cellular Senescence and the Senescent Secretory Phenotype: Therapeutic Opportunities","volume":"123","author":"Tchkonia","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41577-019-0180-1","article-title":"Mechanisms Underlying T Cell Ageing","volume":"19","author":"Goronzy","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1126\/science.aax0860","article-title":"T Cells with Dysfunctional Mitochondria Induce Multimorbidity and Premature Senescence","volume":"368","author":"Aranda","year":"2020","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.chom.2017.03.002","article-title":"Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction","volume":"21","author":"Thevaranjan","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nrneph.2013.44","article-title":"Immune Cell Dysfunction and Inflammation in End-Stage Renal Disease","volume":"9","author":"Betjes","year":"2013","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Betjes, M.G. (2020). Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses. Toxins, 12.","DOI":"10.3390\/toxins12040224"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1038\/s41591-024-03043-1","article-title":"IL-6 Inhibition with Clazakizumab in Patients Receiving Maintenance Dialysis: A Randomized Phase 2b Trial","volume":"30","author":"Chertow","year":"2024","journal-title":"Nat. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Dahdal, S., Saison, C., Valette, M., Bachy, E., Pallet, N., Lina, B., Koenig, A., Monneret, G., Defrance, T., and Morelon, E. (2018). Residual Activatability of Circulating Tfh17 Predicts Humoral Response to Thymodependent Antigens in Patients on Therapeutic Immunosuppression. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.03178"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1039\/C7AY00054E","article-title":"Effect of Sample Temperature, pH, and Matrix on the Percentage Protein Binding of Protein-Bound Uraemic Toxins","volume":"9","author":"Deltombe","year":"2017","journal-title":"Anal. Methods"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/2\/104\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T16:01:47Z","timestamp":1771516907000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/2\/104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":57,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["toxins18020104"],"URL":"https:\/\/doi.org\/10.3390\/toxins18020104","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]}}}