Frontiers in Immunology最新文献

{"title":"Increased serum human epididymis protein 4 is associated with disease activity and systemic involvement in pediatric-onset systemic lupus erythematosus","authors":"Chenxi Liu, Lingyi Yan, Menglan Zhang, Yifei Duan, Jie Luo, Zhijun Liu, Ting Liu, Jiyu Tong, Yongmei Jiang","doi":"10.3389/fimmu.2024.1461987","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1461987","url":null,"abstract":"ObjectiveWe aimed to investigate human epididymis protein 4 (HE4) as a potential biomarker in patients with pediatric-onset systemic lupus erythematosus (pSLE), particularly on the association of serum HE4 levels with disease activity and other laboratory tests.MethodsWe included 137 patients with pSLE and 75 age- and sex-matched healthy controls (HCs). Serum HE4 level was measured by a chemiluminescent microparticle on an Abbott ARCHITECT i2000SR Immunoassay Analyzer. Comparisons between groups were performed using the independent Student t-test, Mann–Whitney U test, Chi-square test, or Fisher’s exact test, as appropriate. We also determined the relationships between HE4 and clinical parameters and evaluated disease activity using SLE Disease Activity Index (SLEDAI) and renal SLEDAI (rSLEDAI).ResultsSerum HE4 levels in patients with pSLE (44.6 pmol/L; IQR, 32.5–73.5) were significantly higher than those in HCs (38.9 pmol/L; IQR, 34–46.1). HE4 levels were significantly higher in moderate to severe disease activities (57.4 pmol/L, IQR 37.7–164.5) than in mild disease activities (38.8 pmol/L, IQR 30.1–48.5) or HCs (38.9 pmol/L, IQR 34.0–46.1), as well as in active renal disease activities (77.2 pmol/L, IQR 47.4–224.1) than in inactive renal disease activities (36.1 pmol/L, IQR 27.8–46.7). The ROC curve analysis showed that HE4 could discriminate pSLE with renal (AUC, 0.717; 95% CI, 0.632–0.801), hematological (AUC, 0.740; 95% CI, 0.648–0.831), and cardiovascular involvement (AUC:0.775, 95% CI 0.669–0.880). Serum HE4 levels significantly correlated with several indicators related to renal morbidity, such as creatinine, blood urea nitrogen, uric acid, cystatin C, urine protein/24 h, etc.ConclusionSerum HE4 levels in pSLE were elevated and highly associated with disease activity and systemic involvement, indicating HE4 as a potential biomarker for pSLE.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Into the storm: the imbalance in the yin-yang immune response as the commonality of cytokine storm syndromes","authors":"Amy Armstrong, Yuting Tang, Neelam Mukherjee, Nu Zhang, Gang Huang","doi":"10.3389/fimmu.2024.1448201","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1448201","url":null,"abstract":"There is a continuous cycle of activation and contraction in the immune response against pathogens and other threats to human health in life. This intrinsic yin-yang of the immune response ensures that inflammatory processes can be appropriately controlled once that threat has been resolved, preventing unnecessary tissue and organ damage. Various factors may contribute to a state of perpetual immune activation, leading to a failure to undergo immune contraction and development of cytokine storm syndromes. A literature review was performed to consider how the trajectory of the immune response in certain individuals leads to cytokine storm, hyperinflammation, and multiorgan damage seen in cytokine storm syndromes. The goal of this review is to evaluate how underlying factors contribute to cytokine storm syndromes, as well as the symptomatology, pathology, and long-term implications of these conditions. Although the recognition of cytokine storm syndromes allows for universal treatment with steroids, this therapy shows limitations for symptom resolution and survival. By identifying cytokine storm syndromes as a continuum of disease, this will allow for a thorough evaluation of disease pathogenesis, consideration of targeted therapies, and eventual restoration of the balance in the yin-yang immune response.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variation in worldwide incidence of Guillain-Barré syndrome: a population-based study in urban China and existing global evidence","authors":"Lu Xu, Chen Zhao, Yutong Bao, Yuchen Liu, Yuqing Liang, Jiyu Wei, Guozhen Liu, Jinxi Wang, Siyan Zhan, Shengfeng Wang, Dongsheng Fan","doi":"10.3389/fimmu.2024.1415986","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1415986","url":null,"abstract":"Background and objectivesGeographical variation existed in the incidences of Guillain-Barré syndrome (GBS), but no national population-based study has evaluated the incidences of GBS in China. This study aimed to estimate the incidence of GBS in urban China and evaluate the worldwide variation in the incidence of GBS.MethodsFirstly, we did a population-based study to calculate the incidence of GBS in urban China based on the National Urban Medical Insurance database from 2013 to 2017. To identify GBS cases, natural language processing was used first for handling the lengthy and unstructured diagnostic information and then checked by prestigious neurologists. Secondly, a systematic review and meta-analysis were performed to analyze the incidence of GBS worldwide. Up to July 4, 2022, Medline, Embase, and Web of Science were retrieved to identify the population-based studies regarding the incidence of GBS. The basic information and the statistics regarding incidence were extracted. Quality assessment considered sample representativeness, condition assessment, and statistical methods.ResultsA total of 1.44 billion person-years in insurance data was covered, with 3,534 GBS cases identified. The annual incidences of GBS in urban China between 2013 and 2017 ranged from 0.41 (95% CI: 0.27 to 0.58) to 0.58 (95% CI: 0.38 to 0.82) per 100,000 person-years. The incidence was the highest in Northwest China and the lowest in Northeast China. The meta-analysis included 122 articles. The quality assessment showed that the quality scores of 43.3% of studies were ≥ 0.75 (the total score is 1). The global incidence of GBS was 1.12 (95% CI: 0.98 to 1.27) per 100,000 person-years. The incidences in West Europe, South Asia, and North Europe were higher, while the incidences in Australia and New Zealand, Southeast Asia, and North Africa were lower. The incidence of enteric infections was positively associated with the incidence of GBS (coefficient=0.0000185, P=0.007). The incidence in Europe, Australia, and America rose significantly from 1960 to 2020 (coefficient=0.01, t=2.52, P=0.015).DiscussionThere is a clear regional variation of the GBS incidence at both national and global levels. Careful control of enteric infections should be conducted to reduce the disease burden.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report: Breaking CNS immuno-privilege: TNFα-inhibitor triggers aseptic meningitis in a patient with rheumatoid arthritis","authors":"Benedetta Kassabian, Monica Facco, Alessandro Miscioscia, Samuela Carraro, Francesca Rinaldi, Paolo Gallo, Marco Puthenparampil","doi":"10.3389/fimmu.2024.1432360","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1432360","url":null,"abstract":"Blood-brain barrier dysfunction might be driven by peripheral inflammation. TNFα inhibitors (TNF-α<jats:sub>i</jats:sub>) are occasionally associated with a wide spectrum of neurological immuno-mediated disorders. However, patients with systemic autoimmune disorders, including rheumatoid arthritis (RA), might be prone to develop further organ-specific, including central nervous system (CNS), autoimmunity. Here we report the case of a patient, affected by RA and treated with etanercept, who suddenly developed focal neurological symptoms. Cerebrospinal fluid, magnetic resonance imaging (MRI), and positron emission tomography (PET)/MRI findings are reported and support the diagnosis of TNF-α<jats:sub>i</jats:sub> -associated aseptic meningitis.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report: Timing of eculizumab treatment in catastrophic antiphospholipid syndrome","authors":"Camillo Carrara, Blerina Mataj, Sara Gastoldi, Piero Ruggenenti, Savino Sciascia, Dario Roccatello","doi":"10.3389/fimmu.2024.1460317","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1460317","url":null,"abstract":"Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening condition of small-vessel thrombosis with acute multiple-organ involvement and visceral damage. In this report, we present a case of a patient with CAPS who is refractory to conventional therapy. For the first time in a patient with CAPS, marked C5b-9 formation was demonstrated on microvascular endothelial cells, suggesting the usefulness of therapeutic complement inhibition in this setting. Eculizumab, a C5-blocking monoclonal antibody, is remarkably effective in the treatment of different forms of thrombotic microangiopathy by controlling complement system hyperactivation. It halted the “thrombotic storm” and promptly achieved full recovery of thrombocytopenia. However, kidney function did not recover, possibly because eculizumab was administered too late. Conceivably, the timing of treatment is crucial to achieving disease remission before irreversible structural damage occurs in target organs, thereby preventing their complete functional recovery.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating pulmonary and non-infectious complications in common variable immunodeficiency disorders: a UK national multi-centre study","authors":"Heba M. Bintalib, Sofia Grigoriadou, Smita Y. Patel, Leman Mutlu, Kavitha Sooriyakumar, Prashantha Vaitla, Elizabeth McDermott, Elizabeth Drewe, Cathal Steele, Manisha Ahuja, Tomaz Garcez, Mark Gompels, Alexandros Grammatikos, Archana Herwadkar, Rehana Ayub, Neil Halliday, Siobhan O. Burns, John R. Hurst, Sarah Goddard","doi":"10.3389/fimmu.2024.1451813","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1451813","url":null,"abstract":"BackgroundCommon Variable Immunodeficiency Disorders (CVID) encompass a spectrum of immunodeficiency characterised by recurrent infections and diverse non-infectious complications (NICs). This study aimed to describe the clinical features and variation in NICs in CVID with and without interstitial lung disease (ILD) from a large UK national registry population.MethodsRetrospective, cross-sectional data from a UK multicentre database (previously known as UKPIN), categorising patients into those with CVID-ILD and those with NICs related to CVID but without pulmonary involvement (CVID-EP; EP= extra-pulmonary involvement only).Results129 patients were included. Chronic lung diseases, especially CVID-ILD, are prominent complications in complex CVID, occurring in 62% of the cohort. Bronchiectasis was common (64% of the cohort) and associated with greater pulmonary function impairment in patients with CVID-ILD compared to those without bronchiectasis. Lymphadenopathy and the absence of gastrointestinal diseases were significant predictors of ILD in complex CVID. Although the presence of liver disease did not differ significantly between the groups, nearly half of the CVID-ILD patients were found to have liver disease. Patients with CVID-ILD were more likely to receive immunosuppressive treatments such as rituximab and mycophenolate mofetil than the CVID-EP group, indicating greater need for treatment and risk of complications.ConclusionThis study highlights the significant burden of CVID-ILD within the CVID population with NICs only. The lungs emerged as the most frequently affected organ, with ILD and bronchiectasis both highly prevalent. These findings emphasise the necessity of a comprehensive and multidisciplinary approach in managing CVID patients, considering their susceptibility to various comorbidities and complications.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report: Bullous pemphigoid combined with Sjögren’s syndrome complicated by central nervous system infection","authors":"Xing-Yue Chen, Jun Chen, Kun-Lan Long, Peng Ding, Rong Li, Li-Jia Zhi","doi":"10.3389/fimmu.2024.1419054","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1419054","url":null,"abstract":"BackgroundBullous pemphigoid (BP) is the most common autoimmune blistering skin disease in humans, characterized by tense blisters, erosions, urticarial lesions, and itching on normal or erythematous skin. Many autoimmune diseases are considered comorbidities of BP, but clinical case reports of BP complicated by Sjögren’s syndrome are very scarce. Furthermore, cases of central nervous system infection secondary to both autoimmune diseases are even rarer.Case presentationWe report a 74-year-old woman diagnosed with bullous pemphigoid, who showed relief of active lesions after treatment with methylprednisolone and dupilumab injections. However, she was admitted for pulmonary infection during which she was diagnosed with Sjögren’s syndrome (SS). Subsequently, the patient developed altered consciousness, indicating a central nervous system infection. Adjustment of steroid dosage and aggressive antimicrobial therapy led to alleviation of symptoms.ConclusionThe coexistence of autoimmune subepidermal blistering diseases and SS is rare. The role of SS in the pathogenesis of skin lesions is unclear, and the relationship between these blistering diseases and SS remains elusive. Further research is needed to determine whether there are common pathological mechanisms between the two conditions.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal effects of systemic inflammatory proteins on Guillain-Barre Syndrome: insights from genome-wide Mendelian randomization, single-cell RNA sequencing analysis, and network pharmacology","authors":"Jingwen Liu, Renbing Pan","doi":"10.3389/fimmu.2024.1456663","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1456663","url":null,"abstract":"BackgroundEvidence from observational studies indicates that inflammatory proteins play a vital role in Guillain-Barre Syndrome (GBS). Nevertheless, it is unclear how circulating inflammatory proteins are causally associated with GBS. Herein, we conducted a two-sample Mendelian randomization (MR) analysis to systematically explore the causal links of genetically determined systemic inflammatory proteins on GBS.MethodsA total of 8,293 participants of European ancestry were included in a genome-wide association study of 41 inflammatory proteins as instrumental variables. Five MR approaches, encompassing inverse-variance weighted, weighted median, MR-Egger, simple model, and weighted model were employed to explore the causal links between inflammatory proteins and GBS. MR-Egger regression was utilized to explore the pleiotropy. Cochran’s Q statistic was implemented to quantify the heterogeneity. Furthermore, we performed single-cell RNA sequencing analysis and predicted potential drug targets through molecular docking technology.ResultsBy applying MR analysis, four inflammatory proteins causally associated with GBS were identified, encompassing IFN-γ (OR:1.96, 95%CI: 1.02-3.78, P<jats:sub>IVW</jats:sub>=0.045), IL-7 (OR:1.86, 95%CI: 1.07-3.23, P<jats:sub>IVW</jats:sub>=0.029), SCGF-β (OR:1.56, 95%CI: 1.11-2.19, P<jats:sub>IVW</jats:sub>=0.011), and Eotaxin (OR:1.99, 95%CI: 1.01-3.90, P<jats:sub>IVW</jats:sub>=0.046). The sensitivity analysis revealed no evidence of pleiotropy or heterogeneity. Additionally, significant genes were found through single-cell RNA sequencing analysis and several anti-inflammatory or neuroprotective small molecular compounds were identified by utilizing molecular docking technology.ConclusionsOur MR analysis suggested that IFN-γ, IL-7, SCGF-β, and Eotaxin were causally linked to the occurrence and development of GBS. These findings elucidated potential causal associations and highlighted the significance of these inflammatory proteins in the pathogenesis and prospective therapeutic targets for GBS.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness of first-line enfortumab vedotin in addition to pembrolizumab for metastatic urothelial carcinoma in the United States","authors":"Andong Li, Meiyu Wu, Ouyang Xie, Heng Xiang, Kehui Meng, Chongqing Tan, Long Wang, Xiaomin Wan","doi":"10.3389/fimmu.2024.1464092","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1464092","url":null,"abstract":"Background and objectiveThe EV-302 trial found that the combination of enfortumab vedotin (EV) with pembrolizumab significantly improved survival for patients with metastatic urothelial carcinoma (mUC). However, given the high cost of the drugs, there is a need to assess its value by considering both efficacy and cost. This study assessed the cost-effectiveness of EV plus pembrolizumab as a first-line treatment for patients with mUC from the perspective of U.S. payers.MethodsA Markov model was developed to compare the lifetime costs and effectiveness of EV in combination with pembrolizumab with chemotherapy in the treatment of mUC patients from U.S. payer perspective. Life-years (LYs), quality-adjusted LYs (QALYs), and lifetime costs were estimated. One-way, two-way and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Additionally, subgroup analyses were performed.ResultsCompared to chemotherapy, the combination of EV and pembrolizumab provided an additional 2.10 LYs and 1.72 QALYs, at an incremental cost of $962,240.8 per patient. The incremental cost-effectiveness ratio (ICER) is $558,973 per QALY. Subgroup analysis indicated that patients ineligible for cisplatin treatment had a lower ICER compared to those who were eligible for cisplatin.ConclusionsFrom the perspective of US payers, at a willingness-to-pay threshold of $150,000 per QALY, the combination of EV and pembrolizumab is estimated to not be cost-effective compared to traditional chemotherapy in the first-line treatment of mUC patients.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic immunostimulation induces glucocorticoid-mediated thymic involution succeeded by rebound hyperplasia which is impaired in aged recipients","authors":"Craig P. Collins, Lam T. Khuat, Gail D. Sckisel, Logan V. Vick, Christine M. Minnar, Cordelia Dunai, Catherine T. Le, Brendan D. Curti, Marka Crittenden, Alexander Merleev, Michael Sheng, Nelson J. Chao, Emanual Maverakis, Spencer R. Rosario, Arta M. Monjazeb, Bruce R. Blazar, Dan L. Longo, Robert J. Canter, William J. Murphy","doi":"10.3389/fimmu.2024.1429912","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1429912","url":null,"abstract":"The thymus is the central organ involved with T-cell development and the production of naïve T cells. During normal aging, the thymus undergoes marked involution, reducing naïve T-cell output and resulting in a predominance of long-lived memory T cells in the periphery. Outside of aging, systemic stress responses that induce corticosteroids (CS), or other insults such as radiation exposure, induce thymocyte apoptosis, resulting in a transient acute thymic involution with subsequent recovery occurring after cessation of the stimulus. Despite the increasing utilization of immunostimulatory regimens in cancer, effects on the thymus and naïve T cell output have not been well characterized. Using both mouse and human systems, the thymic effects of systemic immunostimulatory regimens, such as high dose IL-2 (HD IL-2) with or without agonistic anti-CD40 mAbs and acute primary viral infection, were investigated. These regimens produced a marked acute thymic involution in mice, which correlated with elevated serum glucocorticoid levels and a diminishment of naïve T cells in the periphery. This effect was transient and followed with a rapid thymic “rebound” effect, in which an even greater quantity of thymocytes was observed compared to controls. Similar results were observed in humans, as patients receiving HD IL-2 treatment for cancer demonstrated significantly increased cortisol levels, accompanied by decreased peripheral blood naïve T cells and reduced T-cell receptor excision circles (TRECs), a marker indicative of recent thymic emigrants. Mice adrenalectomized prior to receiving immunotherapy or viral infection demonstrated protection from this glucocorticoid-mediated thymic involution, despite experiencing a substantially higher inflammatory cytokine response and increased immunopathology. Investigation into the effects of immunostimulation on middle aged (7-12 months) and advance aged (22-24 months) mice, which had already undergone significant thymic involution and had a diminished naïve T cell population in the periphery at baseline, revealed that even further involution was incurred. Thymic rebound hyperplasia, however, only occurred in young and middle-aged recipients, while advance aged not only lacked this rebound hyperplasia, but were entirely absent of any indication of thymic restoration. This coincided with prolonged deficits in naïve T cell numbers in advanced aged recipients, further skewing the already memory dominant T cell pool. These results demonstrate that, in both mice and humans, systemic immunostimulatory cancer therapies, as well as immune challenges like subacute viral infections, have the potential to induce profound, but transient, glucocorticoid-mediated thymic involution and substantially reduced thymic output, resulting in the reduction of peripheral naive T cells. This can then be followed by a marked rebound effect with naïve T cell restoration, events that were shown not to occur in advanced-aged mice.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}