Clinical and experimental immunology最新文献

{"title":"Engaging PD-1 rescues regulatory T cell function and inhibits inflammatory T cells in rheumatoid arthritis.","authors":"Kaustav Chowdhury, Uma Kumar, Jaydeep Chaudhuri, Prabin Kumar, Soumabha Das, Maumita Kanjilal, Parasar Ghosh, Ravi Kiran Basyal, Uma Kanga, Santu Bandyopadhaya, Dipendra Kumar Mitra","doi":"10.1093/cei/uxaf035","DOIUrl":"https://doi.org/10.1093/cei/uxaf035","url":null,"abstract":"<p><strong>Background: </strong>Despite their synovial enrichment Regulatory T cells (Treg) fail to alleviate the joint inflammation in rheumatoid arthritis (RA). This indicates their functional impairment in the synovial milieu of RA patients.</p><p><strong>Results: </strong>Here, we demonstrate that deficit in PD-1 pathway incapacitates the synovial Treg cells and engaging PD-1 restores their suppressive function (IL-10, TGF-β secretion) which in turn suppressed the synovial inflammatory T cells (IFN-γ+, IL-17+ TNF-α+). We also showed deficit in programmed death ligand-1 (PD-L1) expression on RA synovial macrophages contributes to impaired Treg cell function.</p><p><strong>Conclusion: </strong>Rejuvenating synovial Treg cell function via PD-1 engagement may be a potential strategy to ameliorate the synovial inflammation in RA patients.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pathophysiology of Hemophagocytic lympho-histiocytosis (HLH) syndrome and insights from animal models.","authors":"Sayan Mukherjee, Puneet Kumar","doi":"10.1093/cei/uxaf036","DOIUrl":"https://doi.org/10.1093/cei/uxaf036","url":null,"abstract":"<p><p>Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by an aberrant immune response against host tissues. It can arise from diverse triggers like infection, inflammation, malignancy, genetic defects, or therapy-related factors. Cytokine storm, capillary leak syndrome, cytokine release syndrome, and macrophage activation syndrome are the different faces of this chimera, and each of them displays significant clinical variability associated with high mortality. The pathogenesis of both primary and secondary HLH generally follows a similar pattern, involving excessive activation of macrophages and uncontrolled destruction of reticuloendothelial tissues. Environmental triggers cause exaggerated activation of innate immune cells in genetically predisposed individuals. This process is further driven by the release of multiple cytokines and soluble mediators that sustain ongoing inflammation and cause subsequent target organ damage. Biomarkers, including cytokines and inflammatory mediators, are crucial for early detection and monitoring treatment response. Persistent immune activation and inadequate resolution mechanisms result in a destructive inflammatory cascade or \"immunological massacre\". Animal models of HLH and MAS elucidate the roles of impaired cytotoxicity, IFN-γ, TLR signaling, and inflammatory cytokines in disease pathogenesis. Trigger-specific differences highlight the involvement of CD8+ T cells, NK cells, macrophages, and cytokines. Therapeutic strategies include cytokine neutralization, adoptive T-cell transfer, and mTOR inhibition. Timely diagnosis and prompt initiation of therapy are essential to mitigate the serious consequences of HLH and improve long-term outcomes.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human genetics of responses to vaccines.","authors":"Eleanor Karp-Tatham, Julian C Knight, Alexandre Bolze","doi":"10.1093/cei/uxaf034","DOIUrl":"https://doi.org/10.1093/cei/uxaf034","url":null,"abstract":"<p><p>The human response to vaccination exhibits considerable variability due to a complex interplay of heritable and environmental factors. This review examines the current understanding of the role of human genetics in vaccine responses, encompassing both rare adverse events following immunization as well as immunogenicity and efficacy . We highlight recent studies including from the COVID-19 pandemic, which provided a unique opportunity to study vaccine genetics at scale for a newly emerging infection and revealed significant associations between HLA alleles and responses to SARS-CoV-2 vaccines. Understanding genetic contributions to vaccine responses holds promise for enhancing vaccine safety and efficacy, and the development of personalized vaccination strategies.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Granulomatous disease: Lessons in Cell Biology From Monogenic Immunodeficiency.","authors":"Paige M Mortimer, Shuli Svetitsky, David C Thomas","doi":"10.1093/cei/uxaf031","DOIUrl":"https://doi.org/10.1093/cei/uxaf031","url":null,"abstract":"<p><p>Reactive oxygen species (ROS) are produced in immune cells by the phagocyte NADPH oxidase (NOX2) system that carries out coordinated transfer of electrons to molecular oxygen. The importance of the system in host defence and immunoregulation is underlined by chronic granulomatous disease (CGD), a severe monogenic immunodeficiency caused by mutations in genes encoding individual components of NOX2. CGD also leads to inflammatory manifestations due to the regulatory role of ROS in multiple signalling processes. We describe the system in detail, from its discovery to our current understanding of the oxidase. We also describe CGD and illustrate how recent insights into this disease shed light on physiology.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1-methyl-tryptophan improves anxiety-like behavior in colitis mice by inhibiting neuroinflammation, promoting cell regeneration and decreasing apoptosis.","authors":"Li-Ping Zhao, Lu-Lu Tan, Yi-Meng Xia, Xiao-Yu Ma, Ting Li, Sheng-Yang Zhou, Jian Wu, Ming-An Li, Wei-Jiang Zhao, Yan-Qin Shen","doi":"10.1093/cei/uxaf030","DOIUrl":"https://doi.org/10.1093/cei/uxaf030","url":null,"abstract":"<p><strong>Introduction: </strong>Mood disorders such as anxiety are important extra-intestinal manifestations of inflammatory bowel disease (IBD), and are more prevalent in active IBD. Studies have shown that pharmacologically-induced anxiety was correlated with changes in plasma Kynurenine (Kyn) concentrations. Our previous study also found that Kyn was abnormally increased in the serum and brain of mice with acute colitis. This study aimed to investigate the role and possible mechanism of Kyn in anxiety-like behavior induced by colitis.</p><p><strong>Methods: </strong>Therefore, we established a 3% Dextran sulfate sodium (DSS)-induced mouse model of acute colitis. Kyn is produced by tryptophan metabolism in the presence of indoleamine 2,3-dioxygenase (IDO, rate-limiting enzyme). Furthermore, 1-methyl-tryptophan (1-MT), as an IDO inhibitor, was used to reduce Kyn synthesis in this study.</p><p><strong>Results: </strong>We found that 1-MT significantly improved anxiety-like behaviors in mice with colitis, as assessed by the marbles burying test. Moreover, our study demonstrated that 1-MT reduced the level of pro-inflammatory cytokine IL-1β and the activation of glial cells in the mouse brain, indicating the anti-inflammatory effect of 1-MT. Similarly, 1-MT inhibited LPS-induced inflammatory responses in BV2 cells, which was consistent with the in vivo results. Furthermore, 1-MT reversed the low expression of DCX and PCNA in the hippocampus caused by colitis, suggesting a pro-neurogenesis and pro-proliferation effect. In addition, we found that Kyn promoted apoptosis by regulating the Bax/Bcl2 signaling cascade through in vitro and in vivo experiments.</p><p><strong>Conclusion: </strong>Overall, these results suggest that 1-MT improved anxiety-like behaviors in mice with colitis by decreasing neuroinflammation, promoting neurogenesis and cell proliferation, and reducing apoptosis.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Senolytic treatment to rescue hallmarks of senescence in lymph node fibroblasts from patients with rheumatoid arthritis: Implications for premature aging and potential therapeutic intervention in early rheumatoid arthritis.","authors":"T A de Jong, J F Semmelink, J W Bolt, C Grasso, R A Hoebe, P M Krawczyk, L G M van Baarsen","doi":"10.1093/cei/uxaf029","DOIUrl":"https://doi.org/10.1093/cei/uxaf029","url":null,"abstract":"<p><strong>Introduction: </strong>Cellular senescence, a state of proliferation arrest, is implicated in the pathogenesis of age-related diseases such as rheumatoid arthritis (RA). The pathogenesis of RA, characterized by immune dysregulation and systemic autoimmunity preceding clinical onset of disease, may involve early accumulation of senescent lymph node (LN) fibroblasts driving immune tolerance breakdown. This study aims to explore the hallmarks of senescence in LN fibroblasts during the earliest phases of RA and evaluate the effects of dasatinib.</p><p><strong>Methods: </strong>Human LN fibroblasts were isolated from inguinal LN needle biopsies from autoantibody-positive individuals at risk of developing RA (RA-risk individuals), RA patients and seronegative healthy volunteers. Senescence hallmarks and the effects of dasatinib treatment were assessed using quantitative PCR, flow cytometry, microscopy, and live-cell imaging.</p><p><strong>Results: </strong>Cell size, granularity and autofluorescence were significantly greater in RA LN fibroblasts compared with controls. Altered gene expression of senescence-associated genes was observed in RA LN fibroblasts. Elevated senescence-associated β-galactosidase activity, more lipofuscin-positive granules and DNA damage were observed in RA-risk and RA LN fibroblasts. Notably, RA(-risk) LN fibroblasts presented impaired DNA damage repair capacity. Dasatinib treatment significantly improved the size and ability of the LN fibroblast pool to repair DNA damage. We observed multiple senescence hallmarks in RA LN fibroblasts and, to a lesser extent, in RA-risk LN fibroblasts, which could be partially restored by senescent cell removal via dasatinib treatment.</p><p><strong>Conclusion: </strong>These findings suggest a role for senescent LN fibroblasts in RA pathogenesis and highlights the potential of dasatinib as a potential therapeutic intervention to mitigate senescence-associated defects in RA.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinctive TCR repertoire in PIMS-TS/MIS-C patients: possible thymus involvement.","authors":"Diana C Yanez, Jasmine Rowell, Maximillian Woodall, Stuart Adams, Lauran O'Neill, Konstantinos Mengrelis, Ching-In Lau, Susan Ross, Sarah Benkenstein, Kate Plant, Claire M Smith, Benny Chain, Mark J Peters, Tessa Crompton","doi":"10.1093/cei/uxaf027","DOIUrl":"https://doi.org/10.1093/cei/uxaf027","url":null,"abstract":"<p><p>During the COVID-19 pandemic a rare new paediatric inflammatory condition (paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS)/MIS-C) was identified which correlated with previous or recent SARS-CoV-2 infection. PIMS-TS led to severe multi-organ inflammation, suggestive of disruption of central tolerance and thymus function. Here we investigated the possible role of the thymus in paediatric PIMS-TS. We confirmed that human thymus explants can be infected with SARS-CoV-2 in vitro. Comparison of T-cell populations in blood from PIMS-TS patients and age-matched healthy control children showed that although the overall proportions of CD4 and CD8 T-cell populations were decreased in PIMS-TS patients, the proportion of naïve cells in the CD4 population was higher in the PIMS-TS group. In PIMS-TS patients, the number of TREC in PBMC correlated strongly with the proportion of naive CD4 and CD8 T-cells, whereas this correlation was not present in healthy children. Sequencing rearranged TCRα and TCRβ transcripts from FACS-sorted CD4+CD8-CD3+ and CD4-CD8+CD3+ from blood from PIMS-TS, healthy children, and additionally paediatric severe COVID-19 patients, showed that while all three groups showed similar diversity and distribution, the repertoire of the PIMS-TS and COVID-19 groups had distinctive patterns of TCR gene segment usage and VJ combinatorial usage compared to healthy controls (TRBV11-2xTRBJ2-7, TRBV11-2xTRBJ1-1, TRBV11-2xTRBJ2-5, TRBV11-2xTRBJ2-1; TRBV29-1xTRBJ2-7, TRBV29-1xTRBJ1-1 enriched in PIMS-TS; TRBV7-9xTRBJ1-2, TRAV9-2xTRAJ30 and TRAV26-1xTRAJ39 enriched in COVID-19). The non-productive TCR rearrangements in the PIMS-TS group were also enriched for TRBV11-2, and showed bias towards distal (5'TRAV to 3'TRAJ) TCR gene segment usage, suggesting involvement of the thymus in PIMS-TS.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of IgA and IgG in Mycobacterium tuberculosis infection: A cross-sectional study in Ethiopia.","authors":"Rubiyat E Islam, Meaza Zewdie, Daniel Mussa, Yonas Abebe, Tom H M Ottenhoff, Kees L M C Franken, Fekadu Abebe, Liya Wassie","doi":"10.1093/cei/uxaf001","DOIUrl":"https://doi.org/10.1093/cei/uxaf001","url":null,"abstract":"<p><strong>Introduction: </strong>Despite the high global prevalence of Mycobacterium tuberculosis (Mtb) infection in humans, most infected individuals achieve a stable immunological equilibrium, without showing clinical signs and symptoms of tuberculosis (TB). Although the role of antibodies in TB is assumed to be relatively small compared to cell-mediated immunity, their role in TB has been documented in a few recent studies.</p><p><strong>Methods: </strong>In this cross-sectional study, we quantitated antibody responses to Mtb antigens, lipoarabinomannan (LAM), and heparin-binding hemagglutinin adhesin (HBHA) by determining antigen-specific immunoglobulin A(IgA) and G(IgG) secretion levels using enzyme-linked immunosorbent assay (ELISA) in serum and saliva of pulmonary TB patients (PTB), their household contacts (HHC), and community controls (CC) (determined by QuantiFERON TB Gold assay QFT- test result).</p><p><strong>Results: </strong>The HBHA-specific IgA levels were significantly higher in both saliva and serum in HHC groups compared to PTB patients (P=0.013, P=0.023). Exposed contacts, who were QFT-negative had higher serum HBHA-specific IgA responses compared to PTB patients (P=0.04). QFT-negative HHC and QFT-positive CC showed higher HBHA and LAM-specific IgG responses (P=0.006, P=0.002, P=0.0009, P=0.006, respectively) than PTB patients. Generally, LAM and HBHA-specific IgA levels were significantly higher in saliva compared to serum (P<0.0001) in all study groups.</p><p><strong>Conclusion: </strong>Overall, the observed higher levels of IgA and IgG in controls, and exposed but QFT-negative contacts suggest a correlation with, and perhaps a role for these antibodies in preventing the development of active TB. The findings highlighted the potential involvement of saliva IgA in the immune response to Mtb, underscoring the relevance of mucosal immunity in TB infection.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Concern: Therapeutic effect of farnesylthiosalicylic acid on adjuvant-induced arthritis through suppressed release of inflammatory cytokines.","authors":"","doi":"10.1093/cei/uxae111","DOIUrl":"10.1093/cei/uxae111","url":null,"abstract":"","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mimics and challenging presentations of DADA2.","authors":"Admir Öztürk, Lara Yagci, Serdal Ugurlu","doi":"10.1093/cei/uxaf017","DOIUrl":"10.1093/cei/uxaf017","url":null,"abstract":"<p><p>Deficiency of adenosine deaminase 2 (DADA2) has been a challenging diagnosis to make since it was first described in 2014. The disease represents a wide range of phenotypes. Therefore, it may present with various clinical patterns. Throughout the years, several difficult-to-diagnose cases of DADA2 were reported in the literature. Although several studies and reviews were published regarding different phenotypes and manifestations of DADA2, a review of challenging cases with diverse combinations of DADA2 manifestations was needed to integrate the knowledge from the literature into the clinical practice. Immunological, hematologic, autoinflammatory, and adult-onset polyarteritis-nodosa patterns were reported in the literature as cases challenging to diagnose. In this review, we aim to summarize the challenging case reports from the literature, provide an algorithmic approach for these kinds of presentations, and share our perspective and recommendations on the topic. Diagnosing DADA2 on time is a vital issue for preventing fatal and debilitating vascular events with anti-TNF-alpha therapy. Thus, early testing for DADA2 in suspected cases is recommended. Family history and genetic testing of the patient and the first-degree relatives are essential for accurate diagnosis. Thorough systemic examination and imaging might help detect clinically silent findings of vasculitis. Enzymatic activity of ADA2, when available, is also a key diagnostic tool that complements genetic testing and clinical evaluation.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}