Immunology letters最新文献

{"title":"Longitudinal analysis at pre- and post-flare of T peripheral helper and T follicular helper subsets in patients with systemic lupus erythematosus","authors":"Noriyasu Seki ,&nbsp;Hideto Tsujimoto ,&nbsp;Shuhei Tanemura ,&nbsp;Jun Kikuchi ,&nbsp;Shuntaro Saito ,&nbsp;Kunio Sugahara ,&nbsp;Keiko Yoshimoto ,&nbsp;Mitsuhiro Akiyama ,&nbsp;Tsutomu Takeuchi ,&nbsp;Kenji Chiba ,&nbsp;Yuko Kaneko","doi":"10.1016/j.imlet.2024.106905","DOIUrl":"10.1016/j.imlet.2024.106905","url":null,"abstract":"<div><h3>Objective</h3><p>We focused to analyze the time-course changes at pre- and post-flare of T peripheral helper (Tph) cells and circulating T follicular helper (Tfh) cells in the blood of patients with systemic lupus erythematosus (SLE) with lupus low disease activity state (LLDAS) before flare.</p></div><div><h3>Methods</h3><p>This study included inactive (<em>n</em> = 29) and active (<em>n</em> = 55) patients with SLE. Tph subsets, Tfh subsets, CD11c^hi B cells, and plasma cells in the blood were determined by flow cytometry. The blood levels of cytokines including interferons (IFNs) were measured by electrochemiluminescence assay or cytokine beads array.</p></div><div><h3>Results</h3><p>Active SLE patients exhibited the increased frequency of Tph1, Tph2, Tfh1, and Tfh2 subsets when compared to inactive patients, but no clear changes in the other subsets. During the treatment with medications, Tph1, Tph2, and Tfh2 subsets were significantly reduced along with disease activity and Tph1 and Tph2 subsets were positively correlated with SLE disease activity index (SLEDAI). The time course analysis of patients at pre- and post-flare revealed that in the patients at LLDAS before flare, Tph subsets and Tfh subsets were relatively low levels. At the flare, Tph cells, particularly Tph1 and Tph2 subsets, were increased and correlated with SLEDAI. Furthermore, the blood levels of IFN-α2a, IFN-γ, and IFN-λ1 were low in the patients with LLDAS before flare but these IFNs, particularly IFN-λ1, were increased along with flare.</p></div><div><h3>Conclusion</h3><p>Increased frequency of Tph1 and Tph2 subsets and elevated levels of serum IFN-λ1 are presumably critical for triggering of flare in SLE.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000798/pdfft?md5=95f2f25c37120c3dbbb1de9cdafb4456&pid=1-s2.0-S0165247824000798-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world effectiveness of original BNT162b2 mRNA COVID-19 against symptomatic Omicron infection among children 5–11 years of age in Brazil: A prospective test-negative design study","authors":"Cristina de Oliveira Rodrigues ,&nbsp;Julia Spinardi ,&nbsp;Regis Goulart Rosa ,&nbsp;Maicon Falavigna ,&nbsp;Emanuel Maltempi de Souza ,&nbsp;Josélia Larger Manfio ,&nbsp;Ana Paula de Souza ,&nbsp;Cintia Laura Pereira de Araujo ,&nbsp;Mírian Cohen ,&nbsp;Gynara Rezende Gonzalez do Valle Barbosa ,&nbsp;Fernanda Kelly Romeiro Silva ,&nbsp;Daniel Sganzerla ,&nbsp;Mariana Motta Dias da Silva ,&nbsp;Diogo Ferreira ,&nbsp;Nicolas Taciano Kunkel ,&nbsp;Nathan Iori Camargo ,&nbsp;Jean Carlos Sarturi ,&nbsp;Márcia Cristina Guilhem ,&nbsp;Jaqueline Carvalho de Oliveira ,&nbsp;Caroline Cardoso Lopes ,&nbsp;John M McLaughlin","doi":"10.1016/j.imlet.2024.106903","DOIUrl":"10.1016/j.imlet.2024.106903","url":null,"abstract":"<div><h3>Objective</h3><p>To estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5–11 years of age.</p></div><div><h3>Methods</h3><p>This prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5–11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated.</p></div><div><h3>Results</h3><p>A total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days).</p></div><div><h3>Conclusion</h3><p>In this study with children 5–11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference.</p></div><div><h3>Trial registration number</h3><p>ClinicalTrials.gov number, NCT05403307 (<span><span>https://classic.clinicaltrials.gov/ct2/show/NCT05403307</span><svg><path></path></svg></span>)</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distorted frequency and functionality of natural killer cells in pemphigus vulgaris: A potential therapeutic target","authors":"Vishakha Hooda ,&nbsp;Sujay Khandpur ,&nbsp;Sudheer Arava ,&nbsp;Alpana Sharma","doi":"10.1016/j.imlet.2024.106900","DOIUrl":"10.1016/j.imlet.2024.106900","url":null,"abstract":"<div><p>Pemphigus vulgaris (PV) is a rare autoimmune disorder where autoantibodies target the desmosomal proteins resulting in blistering of oral mucosa and skin. While the pathogenesis of PV is mainly mediated by the adaptive immune system, key players of innate immunity are also emerging. This study outlines the phenotypic as well as functional attributes of NK cells in PV. Through in-depth analysis using flow cytometry we identified an increase in the frequency of CD56⁺ CD3^- NK cells and their subtypes in periphery. Along with this there is an increased frequency of IFNγ⁺ CD56^bright CD16^dim NK cells. mRNA expression of sorted NK cells for differentially expressed genes, particularly key transcription factors such as T-bet and EOMES, as well as surface receptors like NKG2D and KIR2D, and the cytokine IFNγ, displayed significant upregulation. A significant activation of NK cells was seen in the disease state. The levels of perforin and IFNγ were significantly elevated in the culture supernatants of patients. Additionally, a significantly higher cytotoxicity of NK cells in PV was observed. In lesioned tissues of PV, NK related markers were significantly increased. Lastly, we observed NK cells using confocal microscopy in the tissue biopsies of patients which showed significant infiltration of CD56⁺ CD3^- NK cells at the lesional sites. This study aimed to shed light on the pivotal role of NK cells in the immunopathology of PV, offering a thorough understanding of their behaviour and changes in expression which might help in contributing to the development of novel therapeutics.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoregulatory properties of melatonin in the humoral immune system: A narrative review","authors":"Juan R. Calvo,&nbsp;María D. Maldonado","doi":"10.1016/j.imlet.2024.106901","DOIUrl":"10.1016/j.imlet.2024.106901","url":null,"abstract":"<div><p>Melatonin is the major product both synthesized and secreted by the pineal gland during the night period and it is the principal chronobiotic hormone that regulates the circadian rhythms and seasonal changes in vertebrate biology. Moreover, melatonin shows both a broad distribution along the phylogenetically distant organisms and a high functional versatility. At the present time, a significant amount of experimental evidence has been reported in scientific literature and has clearly shown a functional relationship between the endocrine, nervous, and immune systems. The biochemistry basis of the functional communication between these systems is the utilization of a common chemicals signals. In this framework, at present melatonin is considered to be a relevant member of the so-called neuro-endocrine-immunological network. Thus, both <em>in vivo</em> and <em>in vitro</em> investigations conducted in both experimental animals and humans, have clearly documented that melatonin has an important immunomodulatory role. However, most of the published results refer to information on T lymphocytes, i.e., cell-mediated immunity. On the contrary, fewer studies have been carried out on B lymphocytes, the cells responsible for the so-called humoral immunity. In this review, we have focused on the biological role of melatonin in the humoral immunity. More precisely, we report the actions of melatonin on B lymphocytes biology and on the production of different types of antibodies.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000750/pdfft?md5=3319480193ab6353a25cf11ff9d090bd&pid=1-s2.0-S0165247824000750-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteasome isoforms in human thymi and mouse models","authors":"Michele Mishto ,&nbsp;Iina Takala ,&nbsp;Paola Bonfanti ,&nbsp;Juliane Liepe","doi":"10.1016/j.imlet.2024.106899","DOIUrl":"10.1016/j.imlet.2024.106899","url":null,"abstract":"<div><p>The thymus is the organ where functional and self-tolerant T cells are selected through processes of positive and negative selection before migrating to the periphery. The antigenic peptides presented on MHC class I molecules of thymic epithelial cells (TECs) in the cortex and medulla of the thymus are key players in these processes. It has been theorized that these cells express different proteasome isoforms, which generate MHC class I immunopeptidomes with features that differentiate cortex and medulla, and hence positive and negative CD8⁺ T cell selection. This theory is largely based on mouse models and does not consider the large variety of noncanonical antigenic peptides that could be produced by proteasomes and presented on MHC class I molecules. Here, we review the multi-omics, biochemical and cellular studies carried out on mouse models and human thymi to investigate their content of proteasome isoforms, briefly summarize the implication that noncanonical antigenic peptide presentation in the thymus could have on CD8⁺ T cell repertoire and put these aspects in the larger framework of anatomical and immunological differences between these two species.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000737/pdfft?md5=3e943048eda13db0bd557ee9b6e6a8e4&pid=1-s2.0-S0165247824000737-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatic ductal adenocarcinoma microenvironment: Soluble factors and cancer associated fibroblasts as modulators of NK cell functions","authors":"Simona Carlomagno ,&nbsp;Chiara Setti ,&nbsp;Fulvia Ortolani ,&nbsp;Simona Sivori","doi":"10.1016/j.imlet.2024.106898","DOIUrl":"10.1016/j.imlet.2024.106898","url":null,"abstract":"<div><p>Pancreatic Ductal Adenocarcinoma (PDAC) is the most frequent pancreatic cancer and represents one of the most aggressive human neoplasms. Typically identified at advance stage disease, most PDAC tumors are unresectable and resistant to standard therapies.</p><p>The immunosuppressive microenvironment in PDAC impedes tumor control but a greater understanding of the complex stromal interactions within the tumor microenvironment (TME) and the development of strategies capable of restoring antitumor effector immune responses could be crucial to fight this aggressive tumor and its spread.</p><p>Natural Killer (NK) cells play a crucial role in cancer immunosurveillance and represent an attractive target for immunotherapies, both as cell therapy and as a pharmaceutical target.</p><p>This review describes some crucial components of the PDAC TME (collagens, soluble factors and fibroblasts) that can influence the presence, phenotype and function of NK cells in PDAC patients tumor tissue. This focused overview highlights the therapeutic relevance of dissecting the complex stromal composition to define new strategies for NK cell-based immunotherapies to improve the treatment of PDAC.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000725/pdfft?md5=1cee54f597dfb21e34be3f9d73cb0dd4&pid=1-s2.0-S0165247824000725-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D3 attenuates autoimmune thyroiditis by regulating Th17/Treg cell differentiation via YAP/JAK1/STAT1 axis","authors":"","doi":"10.1016/j.imlet.2024.106890","DOIUrl":"10.1016/j.imlet.2024.106890","url":null,"abstract":"<div><h3>Background</h3><p>Autoimmune thyroiditis (AITD) is an organ-specific autoimmune disease. Substantial evidence suggests that Vitamin D (VitD) deficiency is closely associated with an increased risk of AITD. However, the effects of VitD3 on immune cells, especially Th17/Treg cell subsets, and the underlying molecular mechanism in AITD have not yet been investigated.</p></div><div><h3>Methods</h3><p>An experimental autoimmune thyroiditis (EAT) mouse model was established with a high-iodine diet. After 8 weeks, thyroid injury was assessed using hematoxylin and eosin (H&amp;E) staining. ELISA was employed to measure serum levels of thyroxine (T3 and T4), thyroid autoimmune antibodies (Tg-Ab and TPO-Ab), and inflammatory cytokines. Flow cytometry and multiplex fluorescence immunohistochemical (mIHC) assays were used to analyze Th17/Treg cell subsets. The CCK-8 and flow cytometry assays were used to determine cell viability and apoptosis.</p></div><div><h3>Results</h3><p>Administration of VitD3 reduced thyroid follicle destruction, decreased lymphocyte infiltration, and lowered T3, T4, Tg-Ab, and TPO-Ab serum levels in EAT mice. VitD3 treatment also reduced the frequency of Th17 cells while promoting the Treg cell subset both in the thyroid tissue and in the splenocytes cultured in vitro. Furthermore, VitD3 administration suppressed the production of inflammatory cytokines in EAT mice. VitD3 was also found to regulate Treg cells' differentiation, viability, and apoptosis. Mechanistically, we discovered that VitD3 treatment upregulated YAP expression and activated the JAK/STAT pathway. Rescue assays confirmed that depletion of YAP counteracted the effects of VitD3 on Treg cell differentiation and function.</p></div><div><h3>Conclusion</h3><p>Vitamin D3 attenuates AITD by modulating Th17/Treg cell balance via regulating the YAP/JAK1/STAT1 axis.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cataloging circulating CD3+CD56+ NKT-like cells through a series of stimulating (NKG2D and DNAM-1) and inhibitory (PD-1, TIGIT, and Tim-3) immune checkpoint receptors in women diagnosed with precancerous cervical lesions or invasive cervical carcinoma","authors":"","doi":"10.1016/j.imlet.2024.106889","DOIUrl":"10.1016/j.imlet.2024.106889","url":null,"abstract":"<div><p>Persistent human papillomavirus infection is associated with the development of premalignant lesions that can eventually lead to cervical cancer. In this study, we evaluated the expression of activating (NKG2D, DNAM-1) and inhibitory immune checkpoints receptors (PD-1, TIGIT, and Tim-3) in peripheral blood NKT-like (CD3⁺CD56⁺) lymphocytes from patients with cervical carcinoma (CC, n = 19), high-grade lesions (HG, n = 8), low-grade lesions (LG, n = 19) and healthy donors (HD, n = 17) using multiparametric flow cytometry. Dimensional data analysis showed four clusters within the CD3⁺CD56⁺ cells with different patterns of receptor expression. We observed upregulation of CD16 in CC and HG patients in one of the clusters. In another, TIGIT was upregulated, while DNAM-1 was downregulated. Throughout manual gating, we observed that NKT-like cells expressing activating receptors also co-express inhibitory receptors (PD-1 and TIGIT), which can affect the activation of these cells. A deeper characterization of the functional state of the cells may help to clarify their role in cervical cancer, as will the characterization of the NKT-like cells as cytotoxic CD8⁺ T cells or members of type I or type II NKT cells.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro antibody-mediated SARS-CoV-2 infection suppression through human ACE2 receptor blockade","authors":"Priscilla S. Redd ,&nbsp;Alyssa D. Merting ,&nbsp;John D. Klement ,&nbsp;Dakota B. Poschel ,&nbsp;Dafeng Yang ,&nbsp;Kebin Liu","doi":"10.1016/j.imlet.2024.106887","DOIUrl":"10.1016/j.imlet.2024.106887","url":null,"abstract":"<div><p>Vaccines and antibodies that specifically target or neutralize components of the SARS-CoV-2 virus are effective in prevention and treatment of human patients with SARS-CoV-2 infection. However, vaccines and SARS-CoV-2 neutralization antibodies target a subset of epitopes of viral proteins, and the fast evolution of the SARS-CoV-2 virus and the continuing emergence of SARS-CoV-2 variants confer SARS-CoV-2 immune escape from these therapies. ACE2 is the human cell receptor that serves as the entry point for SARS-CoV-2 into human cells and thus is the gatekeeper for SARS-CoV-2 infection of humans. We report here the development of 4G8C11, an anti-human ACE2 receptor monoclonal antibody that recognizes ACE2 on human cell surfaces. We determined that 4G8C11 blocks SARS-CoV-2 and variant infection of ACE2⁺ human cells. Furthermore, 4G8C11 has minimal effects on ACE2 receptor activity. 4G8C11 is therefore a monoclonal antibody for ACE2 receptor detection and potentially an effective immunotherapeutic agent for SARS-CoV-2 and variants.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated Th17/Treg cell axis is correlated with local and systemic immune response in human intermediate uveitis","authors":"Chaman Saini ,&nbsp;Leena Sapra ,&nbsp;Prabhav Puri ,&nbsp;Pradyumna K. Mishra ,&nbsp;Rohan Chawla ,&nbsp;Rupesh K. Srivastava","doi":"10.1016/j.imlet.2024.106888","DOIUrl":"10.1016/j.imlet.2024.106888","url":null,"abstract":"<div><p>Th17/Treg cell balance is essential for immune homeostasis and when disrupted, is associated with the occurrence and development of inflammation in numerous autoimmune diseases. However, its contribution in pathophysiology of uveitis remains unexplored. In this study, we deciphered the role of Th17/Treg cell balance in autoimmune uveitis subjects. Using flow cytometry, we detected the frequencies and absolute count of both Th17 and Treg cells in the aqueous humor and peripheral blood of patients and healthy controls. Our results for the first time reveal a significant increase (<em>p</em> &lt; 0.01 and <em>p</em> &lt; 0.005) in Th17 population alongside a significant decrease (<em>p</em> &lt; 0.001 and <em>p</em> &lt; 0.003) in Treg cell population in both the aqueous humor and PBMCs of uveitis patients. Further we analyzed the expression of Th17-Treg associated genes and cytokines via qPCR and ELISA respectively. These findings align with our flow cytometry results, as evident by a significant (<em>p</em> &lt; 0.002) up-regulation of <em>IL-17</em> and a concurrent down regulation of <em>IL-10</em> at transcriptional levels. Moreover, IL-17A cytokine was found to be substantially high (<em>p</em> &lt; 0.001) and IL-10 (<em>p</em> &lt; 0.02) down regulated in serum. Interestingly, we demonstrated a significant correlation of Th17/Treg cells in aqueous humor with those in peripheral blood. Conclusively, our results suggest the pivotal role of Th17/Treg cell axis in the immuno-pathophysiology of human uveitis. Further we propose the therapeutic potential of targeting this novel axis for ameliorating the disease burden associated with uveitis.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}