Immunologic Research最新文献

{"title":"Functional and phenotypic changes in natural killer cells expressing immune checkpoint receptors PD-1, CTLA-4, LAG-3, and TIGIT in non-small cell lung cancer: the comparative analysis of tumor microenvironment, peripheral venous blood, and tumor-draining veins.","authors":"Fehim Esen, Duygu Ilke Cikman, Ayse Engin, Akif Turna, Sebnem Batur, Buge Oz, Hande Zeynep Turna, Gunnur Deniz, Esin Aktas Cetin","doi":"10.1007/s12026-024-09573-7","DOIUrl":"10.1007/s12026-024-09573-7","url":null,"abstract":"<p><p>Natural killer (NK) cells are a cytotoxic subset of innate lymphoid cells and have key roles in antitumoral immunity. This study evaluates the roles of immune checkpoint receptors on NK cell phenotype and functions both before and after circulation through tumor tissue. Twenty non-small cell lung cancer patients undergoing surgery and 21 healthy controls were included. Lymphocytes were isolated from peripheral venous blood, tumor-draining venous blood, and tumor tissue. Immune checkpoint receptor (ICR) expressions, intracellular cytokines, and cytotoxic capacity of NK cell subsets were analyzed by flow cytometry. Circulatory levels of sPD-1, sCTLA-4, sLAG-3, and sTIGIT were determined by ELISA. PD-1, CTLA-4, and LAG-3 expressions of both cytotoxic (CD56^neg/dimCD16^bright) and cytokine-producing (CD56^bright/dimCD16^neg) NK cells increased in tumor tissue compared to both peripheral and tumor-draining veins. NK cells expressing PD-1, CTLA-4, or LAG-3 had significantly lower IFN- <math><mi>γ</mi></math> and TNF- <math><mi>α</mi></math> and increased IL-10 expressions in tumor tissue compared to peripheral venous blood. The cytotoxic activity (perforin and granzyme A expressions) of NK cells from tumor tissue was significantly reduced compared to peripheral blood. Soluble ICRs decreased in peripheral blood and tumor-draining vein of the patients compared to peripheral blood of healthy individuals. However, NK cell phenotype and functions were similar in peripheral blood and tumor-draining vein. NSCLC tumor microenvironment impacts ICR expressions in NK cells, and ICR-expressing NK cells have impaired inflammatory cytokine secretion and cytotoxic activities with a regulatory phenotype. However, tumor-draining venous blood did not reflect the immune status of the tumor tissue.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"18"},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853999","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":"SARS-CoV-2 pathophysiology and post-vaccination severity: a systematic review.","authors":"Vanshika Rustagi, Shradheya R R Gupta, Chandni Talwar, Archana Singh, Zhen-Zhu Xiao, Rahul Jamwal, Kiran Bala, Akash Kumar Bhaskar, Shekhar Nagar, Indrakant K Singh","doi":"10.1007/s12026-024-09553-x","DOIUrl":"10.1007/s12026-024-09553-x","url":null,"abstract":"<p><p>Currently, COVID-19 is still striking after 4 years of prevalence, with millions of cases and thousands of fatalities being recorded every month. The virus can impact other major organ systems, including the gastrointestinal tract (GIT), cardiovascular, central nervous system, renal, and hepatobiliary systems. The resulting organ dysfunction from SARS-CoV-2 may be attributed to one or a combination of mechanisms, such as direct viral toxicity, disruptions in the renin-angiotensin-aldosterone system (RAAS), thrombosis, immune dysregulation, and ischemic injury due to vasculitis. SARS-CoV-2 vaccines effectively reduce the severity of the disease, hospitalizations, and mortality. As of October 2024, 13.58 billion vaccine doses have been administered, with an average of 6959 daily doses. Also, the boosters are given after the primary immunization in a homologous and heterologous manner. The vaccines imposed severe potential health side effects such as clotting or obstruction of blood vessels termed arterial or venous thrombosis, autoimmune damage of nerve cells (Guillain-Barré syndrome; GBS), intense activation of coagulation system (vaccine-induced thrombotic thrombocytopenia), acute ischemic stroke (AIS) and cerebral venous sinus thrombosis (CVST), myocarditis, pericarditis, and glomerular disease. Overall, it is essential to highlight that the significant benefits of COVID-19 vaccination far outweigh the low risk of conditions. mRNA-based vaccine technology has emerged as a rapidly deployable vaccine candidate and a viable alternative to existing vaccines. It has a very low probability of adverse health effects, confirmed by data represented by Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Vaccine Adverse Event Reporting System (VAERS), Yellow card approved under CDC, WHO.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"17"},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846603","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":"A patient with CVID-enteropathy successfully treated with ustekinumab.","authors":"Fenella Marley, Melanie Lockett, Mark Gompels, Alexandros Grammatikos","doi":"10.1007/s12026-024-09559-5","DOIUrl":"10.1007/s12026-024-09559-5","url":null,"abstract":"<p><p>CVID (common variable immunodeficiency) is associated with a variety of gastrointestinal disorders including those mimicking Crohn's disease and ulcerative colitis. At present there is no clear trial data for the treatment of CVID enteropathy. There are no specific recommendations for treatment; however, it is commonly treated in a similar manner to inflammatory bowel disease, with corticosteroids, 5-aminosalicylates (5-ASA), azathioprine and anti-TNF therapy all being used. We describe the case of a 54-year-old with CVID-enteropathy presenting with diarrhoea and evidence of granulomatous inflammation on colonic biopsies. He was successfully treated with ustekinumab following failure/intolerance of prednisolone, 5-ASA and azathioprine. Features of CVID-enteropathy improved both clinically and histologically, with no evidence of serious treatment-related side effects.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"19"},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853996","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":"IGF2BP2 promotes lung adenocarcinoma progression by regulating LOX1 and tumor-associated neutrophils.","authors":"Long Qian, Zhuqing Ji, Lingyun Mei, Jun Zhao","doi":"10.1007/s12026-024-09563-9","DOIUrl":"10.1007/s12026-024-09563-9","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is the common form of lung cancer and is prone to distant metastasis. IGF2BP2, an m6A modification regulator, is upregulated in lung cancer tissue, but its specific role within the LUAD tumor microenvironment (TME) is unknown. We explored the role of IGF2BP2 in the progression of LUAD. IGF2BP2 expression in LUAD patient specimens and controls was evaluated through bioinformatics, Western blot, and immunohistochemistry. LUAD subcutaneous and orthotopic xenograft tumor models were established, alongside a co-culture system of tumor-associated neutrophils (TANs) and A549 cells. Functional assays assessed IGF2BP2's role under treatment with JX5, an IGF2BP2 inhibitor. Mechanistic assays explored the interaction between IGF2BP2 and LOX1 in 293T cells. IGF2BP2 was significantly upregulated in LUAD tissues, with higher expression levels predicting worse prognosis for patients (p < 0.001). In subcutaneous and orthotopic xenograft models, treatment with JX5, an IGF2BP2 inhibitor, reduced tumor size, volume, and weight (p < 0.001). JX5 also significantly reduced the concentrations of pro-inflammatory cytokines in peripheral blood (p < 0.01 and p < 0.001). Flow cytometry analysis indicated JX5 reduced CD11b+Ly6G+/CD45+ cells (TANs) in the TME (p < 0.001). Mechanistically, JX5 downregulated LOX1 expression in vivo, and co-culture experiments further demonstrated that IGF2BP2 promotes LUAD progression through LOX1-mediated regulation of TAN activity (p < 0.01 and p < 0.001). Overexpression of LOX1 reversed the inhibitory effects of JX5 on TAN infiltration, tumor cell viability, and apoptosis (p < 0.01 and p < 0.001). Additionally, RNA immunoprecipitation revealed that IGF2BP2 binds to LOX1 mRNA at its m6A modification site, stabilizing LOX1 and enhancing its function in the TME. Knockdown of IGF2BP2 accelerated LOX1 mRNA degradation, confirming its role in maintaining LOX1 stability (p < 0.01 and p < 0.001). IGF2BP2 recognizes and stabilizes LOX1 through m6A modification, contributing to TAN-mediated LUAD progression. Overall, these findings offer new insights into LUAD progression and demonstrate that IGF2BP2 is a key regulator that promotes tumor advancement, highlighting the IGF2BP2-LOX1 axis as a potential therapeutic target for LUAD.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"16"},"PeriodicalIF":3.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835546","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":"Pinocembrin activation of DPP9 inhibits NLRP1 inflammasome activation to alleviate cerebral ischemia/reperfusion-induced lung and intestinal injury.","authors":"Po Wang, Liya Pan, Qianqian Liu, Yan Huang, Youlian Tang, Baoquan Lin, Yayun Liao, Hanwen Luo, Xiaoyan Meng","doi":"10.1007/s12026-024-09580-8","DOIUrl":"10.1007/s12026-024-09580-8","url":null,"abstract":"<p><p>After stroke, there is a high incidence of acute lung injury and impairment of intestinal barrier function. In this research, the effects of pinocembrin on organ injuries induced by cerebral ischemia-reperfusion were investigated in mice with middle cerebral artery occlusion/reperfusion (MCAO/R) and further explored the possible mechanism. The potential targets of pinocembrin against MCAO/R were obtained by online tools. An MCAO/R model was developed in C57BL/6 J mice, in combination with pinocembrin administration and lentivirus-mediated gene intervention. Pinocembrin alleviated neurological impairment, reduced the volume of cerebral infarction, attenuated pathological injury of brain tissues in MCAO/R-induced mice by promoting the expression of dipeptidyl peptidase 9 (DPP9), and blocked the nucleotide-binding domain leucine-rich repeat pyrin domain containing 1 (NLRP1) inflammasome activation. Moreover, pinocembrin attenuated the infiltration of inflammatory cells in the lungs and intestinal histopathological injury induced by MCAO/R. The above effects of pinocembrin were reversed by knocking down DPP9. These findings indicated that pinocembrin inhibits NLRP1 inflammasome activation by inducing DPP9, thus mitigating brain, lung, and intestinal injuries induced by MCAO/R.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"13"},"PeriodicalIF":3.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828381","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":"Selective IgM deficiency: evaluation of 75 patients according to different diagnostic criteria.","authors":"Caroline Hamati Rosa Batista, Maria Carolina Martins Smanio, Pedro Borghesi Poltronieri, Leticia Leme Resende, Cristina Maria Kokron, Myrthes Toledo Barros, Rosana Camara Agondi, Natasha R Ferraroni, Pérsio Roxo-Junior, Mariana Paes Leme Ferriani, Herberto Chong-Neto, Nelson Rosario Filho, Tsukiyo Obu Kamoi, Regina Di Gesu, Ekaterini Goudouris, Carolina Sanchez Aranda, Eli Mansour, Marina T Henriques, Maine L D Bardou, Heinrikki G Antila, Anete Sevciovic Grumach","doi":"10.1007/s12026-024-09568-4","DOIUrl":"10.1007/s12026-024-09568-4","url":null,"abstract":"<p><p>Selective IgM deficiency (SIgMD) has recently been included in the inborn errors of immunity classification. SIgMD has conflicting diagnostic criteria and diverse clinical and immunological findings. We aimed to assess the clinical and laboratory profiles of patients with SIgMD and to compare the data of patients diagnosed using two inclusion criteria. This was a descriptive, retrospective, observational, collaborative study. Patients were included according to the following definitions: Group 1, IgM levels < 0.20 g/L in children and < 0.30 g/L in adults, and Group 2, serum IgM levels below 2SD and, for both, absence of associated immunological diseases or secondary causes. The protocol was approved by the Ethics Committee, and patients provided consent. In total, 75 patients were included: 37 (16 M:21F; mean age, 52.92) and 38 (13 M:25F; mean age, 53.47) in Groups 1 and 2, respectively. The most frequent clinical manifestations were allergic rhinitis (G1, 45.9%; G2, 36.8%), asthma (G1, 37.8%; G2, 28.9%), and pulmonary infections (G1, 27.03%; G2, 21.05%). Chromosomopathies (16.22%) and neoplasia (13.51%) were more frequent in G1, whereas URTI (23.68%) and skin infections (23.68%) were more common in G2. There was no difference in sex or mean age at symptom onset between both groups of patients. Regarding the clinical picture, 90.7% of the lesions were benign (68/75). Chromosomopathies may be associated with SIgMD, suggesting the need to quantify serum IgM levels in these cases. Considering the possibility of developing autoimmunity, neoplasia, and common variable immunodeficiency, it is advisable to follow up patients with SIgMD.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"15"},"PeriodicalIF":3.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828384","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 treatment of triple-negative breast cancer cells with an extract from the Coriolus versicolor mushroom changes macrophage properties related to tumourigenesis.","authors":"Tomasz Jędrzejewski, Justyna Sobocińska, Bartosz Maciejewski, Paulina Spisz, Justyna Walczak-Skierska, Paweł Pomastowski, Sylwia Wrotek","doi":"10.1007/s12026-024-09574-6","DOIUrl":"10.1007/s12026-024-09574-6","url":null,"abstract":"<p><p>Macrophages, the most abundant cells that participate in tumour progression, are the subject of a number of anticancer therapy approaches. Our previous results revealed that an extract of the fungus Coriolus versicolor (CV) has anti-cancer and immunomodulatory properties. The aim of the present study was to investigate whether CV extract-treated triple-negative breast cancer (TNBC) cells can release factors that can reprogram macrophages from pro-tumourigenic to anti-cancer subtypes. RAW 264.7 macrophages were cultured in a conditioned medium (CM) from non-treated 4T1 breast cancer cells (CM-NT) or CV extract-stimulated cells (CM-CV). After treatment, the following macrophage properties were evaluated: cell viability; M1/M2 phenotype (enzyme activities: iNOS and arginase 1; and expression of CD molecules: CD80 and CD163); cytokine concentrations: IL-6, TNF-α, IL-10, TGF-β, MCP-1 and VEGF; migration level; and ROS production. The results revealed that, compared with normal cells, TNBC cells stimulated with CV extract create a microenvironment that promotes a decrease in macrophage viability and migration, intracellular ROS production, and pro-angiogenic cytokine production (VEGF and MCP-1). Moreover, CM-CV decreased the expression of M2 macrophage markers (arginase 1 and CD163; IL-10 and TGF-β) but upregulated the expression of M1 cell markers (iNOS and CD80; IL-6 and TNF-α). We concluded that CV extract modifies the tumour microenvironment and changes macrophage polarisation toward functioning as an anti-tumour agent. Therefore, it is promising to use in the treatment of TNBC-associated macrophages.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"14"},"PeriodicalIF":3.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828379","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":"Targeting the neonatal Fc receptor (FcRn) is not beneficial in an animal model of chronic neuritis.","authors":"Anne K Mausberg, Fabian Szepanowski, Bianca Eggert, Kai C Liebig, Christoph Kleinschnitz, Bernd C Kieseier, Mark Stettner","doi":"10.1007/s12026-024-09565-7","DOIUrl":"10.1007/s12026-024-09565-7","url":null,"abstract":"<p><p>The inhibition of the neonatal Fc receptor (FcRn) is a promising therapeutic pathway in certain autoimmune disorders to reduce the amount of circulating pathogenic IgG autoantibodies by interfering with their recycling system. FcRn antibodies are currently being tested in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). This study aimed to investigate the therapeutic potential of an antibody targeting FcRn in the intracellular adhesion molecule 1 (ICAM1)-deficient NOD mouse-a model representative for many aspects of human CIDP. After the onset of clinical signs of neuropathy, ICAM1-deficient NOD mice were assigned to treatment twice per week with anti-FcRn antibody, isotype control antibody (negative control) or intraperitoneal (administered) immunoglobulin (positive control). Disease severity was monitored using disease-specific assessments for ataxia and paresis such as grip strength measurements. Serum immunoglobulin levels and peripheral nerve immune cell infiltration were quantified. Treatment with anti-FcRn antibody did not ameliorate disease progression, as determined by clinical scores and grip strength analysis. Disease progression was reduced in the positive control animals receiving immunoglobulin. Consistent with the clinical results, the composition of infiltrating immune cells was not altered in the peripheral nerve of anti-FcRn antibody-treated mice compared to controls. However, in anti-FcRn antibody-treated mice, significantly lower IgG levels were detectable compared to controls. These findings suggest that targeting the FcRn recycling system does not influence disease progression in the NOD-ICAM1-deficient mouse model of CIDP. Further studies will elucidate whether the reduction of IgG levels was insufficient to deplete pathogenic autoantibodies or whether the major inflammatory driver in the NOD-ICAM1-deficient mouse animal model is mediated by factors other than pathological immunoglobulins.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"12"},"PeriodicalIF":3.3,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828386","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":"Prognostic value of myeloid-derived suppressor-like cells in acute myeloid leukemia: insights from immunophenotyping and clinical correlations.","authors":"Alexia N Sant'Ana, Camila K Dias, Vitória B S Nunes, Mariela G Farias, Ana P Alegretti, Pâmela Portela, Ebellins T Calvache, Maria F Meirelles, Liane E Daudt, Mariana B Michalowski, Alessandra A Paz, Fabrício Figueiró","doi":"10.1007/s12026-024-09558-6","DOIUrl":"10.1007/s12026-024-09558-6","url":null,"abstract":"<p><p>Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population that acts on both innate and adaptive immunity, fostering immune escape in tumors and contributing to cancer progression. Despite the lack of definitive markers for immunophenotyping MDSCs, particularly the polymorphonuclear (PMN-MDSC) subset, these cells seem to play a crucial role in acute myeloid leukemia (AML) patients' prognosis. Additionally, the maturation stage of MDSCs remains a subject of debate and is largely unknown within the AML context. In this study, we conducted a retrospective analysis of flow cytometry immunophenotyping data obtained at the diagnosis of AML patients. We explored how the enrichment of neutrophil maturation stages, the frequency of PMN-MDSC-like cells and monocytic MDSC-like population (M-MDSC-like), and the ratios of MDSC-like cells to T lymphocytes correlate with relevant prognostic indicators. Our findings revealed that CD45⁺CD33^lowHLA-DR^-CD36⁺ PMN-MDSC-like cells and mature CD13⁺CD11b⁺CD10⁺ neutrophils correlate poor survival in AML patients. Furthermore, PMN-MDSC-like cells, and their ratio to T lymphocytes, are elevated in patients with adverse-risk stratification. Similarly, the M-MDSC-like population is increased in FLT3-ITD mutation carrier patients. Notably, we observed confirmational evidence of CD36 relevance in the AML context, which has emerged recently as a potential marker for PMN-MDSCs. Our study highlights significant findings associating increased MDSC-like subsets and poor prognostic factors in AML.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"11"},"PeriodicalIF":3.3,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824314","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":"USP18-mediated protein stabilization of NOTCH1 is associated with altered Th17/Treg cell ratios and B cell-mediated autoantibody secretion in Sjögren syndrome.","authors":"Xiaorong Jin, Yunjing Bai, Xiaohua Xu, Fan Wu, Xiaoyu Long, Yajuan Yao","doi":"10.1007/s12026-024-09566-6","DOIUrl":"10.1007/s12026-024-09566-6","url":null,"abstract":"<p><p>Sjögren Syndrome (SS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration of exocrine glands. This study, based on bioinformatics predictions, investigates the biological functions of ubiquitin specific peptidase 18 (USP18) and notch receptor 1 (NOTCH1) in T helper 17 (Th17) and regulatory T (Treg) cell imbalance and B cell activity in SS. USP18 and NOTCH1 were highly expressed in peripheral blood mononuclear cells (PBMCs) of SS patients and the PBMCs of NOD mice compared to the controls. Adenovirus-mediated knockdown of USP18 significantly enhanced the salivary flow rate of NOD mice while reducing lymphocyte infiltration in mouse salivary ligand tissues. In addition, it decreased the proportions of Th17 cells while increasing the proportions of Treg cells. USP18 enhanced NOTCH1 protein stability through de-ubiquitination modification. In the presence of USP18 knockdown, the NOTCH1 upregulation restored the predominance of Th17 cells in mice. In B cells isolated from PBMCs, the production of B cell autoantibodies was decreased by USP18 silencing but enhanced by NOTCH1 upregulation. In summary, this study demonstrates that USP18-mediated protein stabilization of NOTCH1 is correlated with Th17/Treg cell imbalance and B cell activity during SS development.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"10"},"PeriodicalIF":3.3,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822034","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}