Meenu Bhatiya, Surajit Pathak, Ganesan Jothimani, Asim K. Duttaroy, Antara Banerjee
{"title":"A Comprehensive Study on the Anti-cancer Effects of Quercetin and Its Epigenetic Modifications in Arresting Progression of Colon Cancer Cell Proliferation","authors":"Meenu Bhatiya, Surajit Pathak, Ganesan Jothimani, Asim K. Duttaroy, Antara Banerjee","doi":"10.1007/s00005-023-00669-w","DOIUrl":"10.1007/s00005-023-00669-w","url":null,"abstract":"<div><p>Colon cancer etiology involves a wide spectrum of genetic and epigenetic alterations, finding it challenging to find effective therapeutic strategies. Quercetin exhibits potent anti-proliferative/apoptotic properties. In the present study, we aimed to elucidate the anti-cancer and anti-aging effect of quercetin in colon cancer cell lines. The anti-proliferative effect of quercetin was assessed in vitro by CCK-8 in normal and colon cancer cell lines. To check the anti-aging potential of quercetin, collagenase, elastase, and hyaluronidase inhibitory activity assays were performed. The epigenetic and DNA damage assays were performed using the human NAD-dependent deacetylase Sirtuin-6, proteasome 20S, Klotho, Cytochrome-C, and telomerase ELISA kits. Furthermore, the aging-associated miRNA expression profiling was performed on colon cancer cells. The treatment with quercetin inhibited cell proliferation of colon cancer cells in a dose-dependent manner. Quercetin arrested colon cancer cell growth by modulating expression of aging proteins including Sirtuin-6 and Klotho and also by inhibiting telomerase activity to restrict the telomere length which is evident from qPCR analysis. Quercetin also exhibited DNA damage protection by reducing proteasome 20S levels. The miRNA expression profiling results displayed differential expression of miRNA in colon cancer cell, and in addition, the highly upregulated miRNA was involved in the regulation of cell cycle, proliferation, and transcription. Our data suggest that quercetin treatment inhibited cell proliferation in colon cancer cells through regulating the anti-aging protein expression and provides better understanding for quercetin’s potential use in colon cancer treatment.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"71 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-023-00669-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10843638","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":"Heterogeneity of Extracellular Vesicles and Particles: Molecular Voxels in the Blood Borne “Hologram” of Organ Function, Dysfunction and Cancer","authors":"Janusz Rak, Leon Strzadala","doi":"10.1007/s00005-023-00671-2","DOIUrl":"10.1007/s00005-023-00671-2","url":null,"abstract":"<div><p>Extracellular vesicles (EVs) and particles (EPs) serve as unique carriers of complex molecular information with increasingly recognized roles in health and disease. Individual EVs/EPs collectively contribute to the molecular fingerprint of their producing cell, reflecting its identity, state, function and phenotype. This property is of particular interest in cancer where enormous heterogeneity of cancer cells is compounded by the presence of altered stromal, vascular and immune cell populations, which is further complicated by systemic responses elicited by the disease in individual patients. These diverse and interacting cellular compartments are dynamically represented by myriads of EVs/EPs released into the circulating biofluids (blood) during cancer progression and treatment. Current approaches of liquid biopsy seek to follow specific elements of the EV/EP cargo that may have diagnostic utility (as biomarkers), such as cancer cell-derived mutant oncoproteins or nucleic acids. However, with emerging technologies enabling high-throughput EV/EP analysis at a single particle level, a more holistic approach may be on the horizon. Indeed, each EV/EP carries multidimensional information (molecular “voxel”) that could be integrated across thousands of particles into a larger and unbiased landscape (EV/EP “hologram”) reflecting the true cellular complexity of the disease, along with cellular interactions, systemic responses and effects of treatment. Thus, the longitudinal molecular mapping of EV/EP populations may add a new dimension to crucial aspects of cancer biology, personalized diagnostics, and therapy.\u0000</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"71 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50002989","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":"Ly-6A-Induced Growth Inhibition and Cell Death in a Transformed CD4+ T Cell Line: Role of Tumor Necrosis Factor-α","authors":"Akshay G. Patel, Sarah Moxham, Anil K. Bamezai","doi":"10.1007/s00005-023-00670-3","DOIUrl":"10.1007/s00005-023-00670-3","url":null,"abstract":"<div><p>Ly-6A, a member of the Ly-6/uPAR supergene family of proteins, is a cell adhesion and cell signaling protein. Signaling through Ly-6A activates the cell-intrinsic apoptotic cell death pathway in CD4<sup>+</sup> T cell lines, as indicated by the release of cytochrome C, and activation of caspases 9 and 3. In addition, Ly-6A induces cytokine production and growth inhibition. The mechanism underlying the distinct cellular responses that are triggered by engaging Ly-6A protein has remained unknown. To examine the relatedness of these distinct responses, we have quantified the production of pro-apoptotic, growth inhibitory and tumor suppressive cytokines, such as TNF-α, TGF-β and a related protein GDF-10, in response to Ly-6A signaling. Anti-Ly-6A monoclonal antibody-induced activation of YH16.33 CD4<sup>+</sup> T cell line generated low levels of TGF-β and GDF-10 but elevated levels of TNF-α. Blocking the biological activity of TNF-α resulted in reduced Ly-6A-induced apoptosis in T cells. The Ly-6A-induced response in the T cell line was distinct, as signaling through the antigen receptor complex did not cause growth inhibition and apoptosis despite high levels of TGF-β and GDF-10 that were detected in these cultures. Additionally, in response to antigen receptor complex signaling, lower amount of TNF-α was detected. These results indicate the contribution of TNF-α in the observed Ly-6A-induced growth inhibition and apoptosis and provide a mechanistic explanation for the biologically distinct responses observed in CD4<sup>+</sup> T cells after engaging Ly-6A protein. Additionally, the findings reported here will aid in the understanding of inhibitory signaling initiated by Ly-6A protein, especially in the context of its potential immune checkpoint inhibitory role in T cells.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"71 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49997645","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}
Philemon D. Shallie, Thajasvarie Naicker, Nihar R. Nayak
{"title":"Stress-Sensitive Regulators of Fetal Neurodevelopment in HIV and Preeclampsia: An Immunocytochemical Appraisal of Placental OGT and T4 Levels","authors":"Philemon D. Shallie, Thajasvarie Naicker, Nihar R. Nayak","doi":"10.1007/s00005-023-00668-x","DOIUrl":"10.1007/s00005-023-00668-x","url":null,"abstract":"<div><p>Preeclampsia and HIV are a significant burden to maternal health globally, especially in low-middle income countries such as South Africa. In the KwaZulu-Natal province, SA antenatal HIV prevalence is 41.1%, while PE is 12%. PE and HIV infections are maternal stress and inflammation that impact placental function and fetal development. Therefore, this study investigated the impact of the comorbidity of PE and HIV on placental stress and neurodevelopment. Placentae were obtained from four cohorts of pregnant women: normotensive HIV negative, normotensive HIV positive, preeclamptic HIV negative, and preeclamptic HIV positive. The placental tissue sections were immunostained for OGT and T4. Our findings showed that the maternal weight, diastolic, and systolic blood pressures (BP) were higher in PE vs. the normotensive groups, irrespective of HIV status. In addition, significant changes were noticed in the placental weight, fetoplacental ratio, and placental efficiency coefficient. Our findings showed that the maternal weight<b>,</b> diastolic, and systolic blood pressures (BP) were statistically higher in the PE compared to the normotensive. No significant differences were observed between HIV positive and HIV negative groups. In addition, significant changes were noticed in the placental weight, fetoplacental ratio, and placental coefficient. Furthermore, considerable upregulation in the placental expression of OGT in both the conducting and exchange villi of PE and concomitant downregulation in HIV-positive patients compared with Normotensive and HIV-negative individuals, respectively<b>.</b> Our results provide inferential evidence on the dysregulation of OGT in the comorbidity of PE and HIV. This may mediate a compromised programmed outcome of an adverse maternal environment during pregnancy and consequently affect fetal development.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"71 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10571415","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}
Blanka Wolszczak-Biedrzycka, Anna Bieńkowska, Elżbieta Zasimowicz, Grzegorz Biedrzycki, Justyna Dorf, Wojciech Jelski
{"title":"An Assessment of the Serum Activity of ADH and ALDH in Patients with Primary Biliary Cholangitis","authors":"Blanka Wolszczak-Biedrzycka, Anna Bieńkowska, Elżbieta Zasimowicz, Grzegorz Biedrzycki, Justyna Dorf, Wojciech Jelski","doi":"10.1007/s00005-022-00667-4","DOIUrl":"10.1007/s00005-022-00667-4","url":null,"abstract":"<div><p>Primary biliary cholangitis (PBC; previously known as primary biliary cirrhosis) is a chronic inflammation-induced cholestatic process in the liver. Antimitochondrial antibodies (AMAs) are observed in around 90% of patients, which suggests that PBC is an autoimmune disease. Alcohol dehydrogenase (ADH), ADH isoenzymes and aldehyde dehydrogenase (ALDH) are localized in the liver, and they are useful markers of liver dysfunction. In this study, the activity of total ADH, ADH isoenzymes and ALDH was evaluated in the blood serum of patients with PBC. The experimental group comprised 50 PBC patients, both male and female, aged 28–67. The control group consisted of 50 healthy subjects, both male and female, aged 25–65. The serum activity of class I ADH, class II ADH and ALDH was measured by spectrofluorophotometry, whereas total ADH and class III ADH activity was determined by photometry methods. The activity of class I ADH and total ADH was significantly higher in the experimental group than in the control group (<i>p</i> < 0.001). An increase in class I ADH and total ADH activity indicates that the isoenzyme class I ADH is released by compromised liver cells and can be useful diagnostic markers of PBC.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"71 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-022-00667-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10446237","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}
David Perna-Barrull, Laia Gomez-Muñoz, Silvia Rodriguez-Fernandez, Anna Gieras, Rosa M. Ampudia-Carrasco, Lidia Almenara-Fuentes, Ruth M. Risueño, Sergi Querol, Eva Tolosa, Marta Vives-Pi
{"title":"Impact of Betamethasone Pretreatment on Engrafment of Cord Blood-Derived Hematopoietic Stem Cells","authors":"David Perna-Barrull, Laia Gomez-Muñoz, Silvia Rodriguez-Fernandez, Anna Gieras, Rosa M. Ampudia-Carrasco, Lidia Almenara-Fuentes, Ruth M. Risueño, Sergi Querol, Eva Tolosa, Marta Vives-Pi","doi":"10.1007/s00005-022-00666-5","DOIUrl":"10.1007/s00005-022-00666-5","url":null,"abstract":"<div><p>Hematopoietic stem cell (HSC) transplantation is crucial to cure hematologic malignancies. Umbilical cord blood (UCB) is a source of stem cells, but 90% of UCB units are discarded due to low cellularity. Improving the engraftment capacities of CD34<sup>+</sup> stem cells would allow the use of UCB that were so far rejected. Betamethasone induces long-term transcriptomic and epigenomic changes in immune cells through glucocorticoid receptor. We hypothesize that discarded UCB could be used owing to improvements induced by betamethasone. Isolated CD34<sup>+</sup> HSC from UCB were exposed to the synthetic glucocorticoids betamethasone and fluticasone for 20 h, and cell phenotype was determined before transplantation. NSG mice were sub-lethally irradiated (1 Gy or 2 Gy) 6 h before intravenously transferring 2–5 × 10<sup>5</sup> CD34<sup>+</sup> HSC. The peripheral blood engraftment levels and the leukocyte subsets were followed up for 20 weeks using flow cytometry. At end point, the engraftment and leukocyte subsets were determined in the spleen and bone marrow. We demonstrated that betamethasone has surprising effects in recovering immune system homeostasis. Betamethasone and fluticasone increase CXCR4 and decrease HLA class II and CD54 expression in CD34<sup>+</sup> HSCs. Both glucocorticoids-exposed cells showed a similar engraftment in 2 Gy-irradiated NSG mice. Interestingly, betamethasone-exposed cells showed enhanced engraftment in 1 Gy-irradiated NSG mice, with a trend to increase regulatory T cell percentage when compared to control. Betamethasone induces alterations in CD34<sup>+</sup> HSCs and improve the engraftment, leading to a faster immune system recovery, which will contribute to engrafted cells survival.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"71 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2022-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-022-00666-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10398039","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":"Application of Metabolomics in Childhood Leukemia Diagnostics","authors":"Agata Kozioł, Małgorzata Pupek","doi":"10.1007/s00005-022-00665-6","DOIUrl":"10.1007/s00005-022-00665-6","url":null,"abstract":"<div><p>Metabolomics is a new field of science dealing with the study and analysis of metabolites formed in living cells. The biological fluids used in this test method are: blood, blood plasma, serum, cerebrospinal fluid, saliva and urine. The most popular methods of assessing the composition of metabolites include nuclear magnetic resonance spectroscopy and mass spectrometry (MS) in combination with gas chromatography–MS or liquid chromatography–MS. Metabolomics is used in many areas of medicine. The variability of biochemical processes in neoplastic cells in relation to healthy cells is the starting point for this type of research. The aim of the research currently being carried out is primarily to find biomarkers for quick diagnosis of the disease, assessment of its advancement and treatment effectiveness. The development of metabolomics may also contribute to the individualization of treatment of patients, adjusting drugs depending on the metabolic profile, and thus may improve the effectiveness of therapy, reduce side effects and help to improve the quality of life of patients. Here, we review the current and potential applications of metabolomics, focusing on its use as a biomarker method for childhood leukemia.</p><h3>Graphic abstract</h3>\u0000 <div><figure><div><div><picture><source><img></source></picture></div></div></figure></div>\u0000 </div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"70 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-022-00665-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40459698","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":"Small Extracellular Vesicles Loaded with Immunosuppressive miRNAs Leads to an Inhibition of Dendritic Cell Maturation","authors":"Liliana Czernek, Łukasz Pęczek, Markus Düchler","doi":"10.1007/s00005-022-00664-7","DOIUrl":"10.1007/s00005-022-00664-7","url":null,"abstract":"<div><p>In particular conditions, inhibition of an immune response is required to prevent tissue damage. Among these conditions are diseases caused by an over-reactive immune response, such as autoimmune or allergic disorders, or imminent organ rejection after transplantation. To avoid tissue damage, drug-mediated systemic immune suppression is an option, but it comes with high costs in the form of susceptibility to viral and bacterial infections. Thus, the induction of antigen-specific tolerance is preferable. Extracellular vesicles (EVs) are capable of delivering antigen together with immunosuppressive signals and may be used to specifically induce antigen-specific tolerance. However, naturally occurring EVs are heterogeneous and not all of them show immunosuppressive character. In our trials to engineer cell culture derived EVs to increase their tolerogenic potential, we equipped them with immunosuppressive miRNA mimics. Small EVs (sEVs) were isolated and purified from the human monocytic THP-1 cell line or from healthy donor peripheral blood mononuclear cells, and electroporated with miR-494 and miR-146a mimics. The acquired immunosuppressive potential of the modified sEVs was demonstrated by their ability to alter the major histocompatibility complex molecules and co-stimulatory receptors present on dendritic cells (DCs). To avoid allogeneic responses, the same cells that produced the sEVs served also as recipient cells. In contrast to the treatment with unmodified sEVs, the tolerogenic sEVs impeded lipopolysaccharide-induced maturation and kept DCs in a more immature developmental stage. Our experiments show that simple manipulations of sEVs using immunosuppressive cargo can lead to the inhibition of DC maturation.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"70 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-022-00664-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40658993","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}
Jan Kowalski, Maciej Nowak, Bartłomiej Górski, Renata Górska
{"title":"What Has Immunology Brought to Periodontal Disease in Recent Years?","authors":"Jan Kowalski, Maciej Nowak, Bartłomiej Górski, Renata Górska","doi":"10.1007/s00005-022-00662-9","DOIUrl":"10.1007/s00005-022-00662-9","url":null,"abstract":"<div><p>Recent decades have shed a new light on the pathomechanism of periodontal inflammation. While classic periodontology concentrates on biofilm control, oral hygiene improvement, professional tooth cleaning and surgical correction of damaged periodontal tissues, new aspects of the destruction mechanisms are being raised. Among them, the greatest attention is paid to the influence of host response on the clinical manifestations of the disease. Numerous studies have proved that the shift from gingivitis to periodontitis is not a simple progress of the disease, but an event occurring only in susceptible individuals. Susceptibility may result from appearance of local factors facilitating biofilm accumulation and/or maturation, or from systemic features, among which over-reaction and prolonged agitation of non-specific component of inflammatory response is crucial. The present paper summarizes the association between periodontology and immunology and updates the knowledge accrued mostly in the recent years. After a brief explanation of advances in understanding of the disease aetiology, the most studied and potentially viable immunological markers of periodontal disease are presented. Possible new therapeutic strategies, exploiting knowledge about the nature of host response—immunomodulation and reduction of chronic oxidative stress—are also presented.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"70 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2022-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-022-00662-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33541474","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}
Ying Gao, Lan Li, Xingxing Hu, Weihua Zhang, Yu Li
{"title":"Interleukin-35 has a Protective Role in Infectious Mononucleosis-Induced Liver Inflammation Probably by Inhibiting CD8+ T Cell Function","authors":"Ying Gao, Lan Li, Xingxing Hu, Weihua Zhang, Yu Li","doi":"10.1007/s00005-022-00663-8","DOIUrl":"10.1007/s00005-022-00663-8","url":null,"abstract":"<div><p>Interleukin (IL)-35 plays an immunosuppressive role in infectious diseases, autoimmune disorders, and cancers. However, IL-35 expression and its regulation of CD8<sup>+</sup> T cells in infectious mononucleosis (IM) are not fully understood. In this study, three groups of participants were compared, including twenty-three patients of IM without liver inflammation, twenty-eight patients of IM with liver inflammation, and twenty-one controls. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated. CD8<sup>+</sup> T cells were purified. Plasma IL-35 was measured by ELISA. PBMCs and CD8<sup>+</sup> T cells were stimulated with recombinant human IL-35 in vitro. Perforin and granzyme B secretion was assessed by ELISPOT. Immune checkpoint molecule expression was investigated by flow cytometry. CD8<sup>+</sup> T cells were co-cultured with HepG2 cells in direct contact and indirect contact manner. The cytotoxicity of CD8<sup>+</sup> T cells was calculated by measuring lactate dehydrogenase release and proinflammatory cytokine expression. There was no significant difference in plasma IL-35 levels between patients with IM without liver inflammation and the controls, but the IL-35 level was notably increased in patients with IM who presented with liver inflammation and negatively correlated with aminotransferase. CD8<sup>+</sup> T cells in patients with IM with liver inflammation showed stronger cytotoxicity. IL-35 stimulation inhibited CD8<sup>+</sup> T cell-induced target cell death in patients with IM, mainly through suppression of IFN-γ/TNF-α secretion and elevation of immune checkpoint molecule expression, but did not affect perforin or granzyme B secretion. The current data indicated that IL-35 dampened the cytotoxicity of CD8<sup>+</sup> T cells in patients with IM probably via repression of cytokine secretion. Elevated IL-35 may protect against CD8<sup>+</sup> T cell-induced liver inflammation in patients with IM.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"70 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50019874","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}