Immunologic ResearchPub Date : 2024-10-01Epub Date: 2024-08-30DOI: 10.1007/s12026-024-09518-0
Maurizio Benucci, Ilaria Di Girolamo, Antonino Di Girolamo, Francesca Li Gobbi, Arianna Damiani, Serena Guiducci, Barbara Lari, Valentina Grossi, Maria Infantino, Mariangela Manfredi
{"title":"Predictive biomarkers of response to tocilizumab in giant cell arteritis (GCA): correlations with imaging activity.","authors":"Maurizio Benucci, Ilaria Di Girolamo, Antonino Di Girolamo, Francesca Li Gobbi, Arianna Damiani, Serena Guiducci, Barbara Lari, Valentina Grossi, Maria Infantino, Mariangela Manfredi","doi":"10.1007/s12026-024-09518-0","DOIUrl":"10.1007/s12026-024-09518-0","url":null,"abstract":"<p><p>In the recent EULAR recommendations, ultrasound examination is now recommended as a first-line imaging test in all patients with suspected giant cell arteritis (GCA) and the axillary arteries should be included in the standard exam. As an alternative to ultrasound evaluation, cranial and extracranial arteries can be examined using FDG-PET or MRI. The aim of our study was to observe in a retrospective case series whether there is a correlation between biomarkers and imaging activity in a population of patients followed in real life with GCA treated with prednisone (PDN) and tocilizumab (TCZ). We retrospectively enrolled 68 patients with newly diagnosed GCA between January 2020 and September 2021, followed in real life, who were examined at the Rheumatology Unit of the San Giovanni di Dio Hospital, Florence, Italy. Patients were evaluated at T0-T3-T6-T12-T18-T24 for the following blood tests: ESR, CRP, fibrinogen, platelet count, serum amyloid A (SAA), IL-6, and circulating calprotectin (MRP). Ultrasound examination of the temporal arteries and axillary arteries was assessed at T0 within 7 days of starting treatment with high-dose glucocorticoids and subsequently at T3-T6-T12-T18-T24. A scale from 0 to 3 with semi-quantitative tools (SUV max) was assessed at T0-T12-T24. The evaluation of the correlation coefficient between laboratory and imaging variables has shown that SAA and MRP have the most powerful correlation with the PET score (0.523 and 0.64), and MRP also has an excellent correlation coefficient with the Halo score (0.658). The evaluation of the ROC curves shows for a PET score 3 and SAA values higher than 26 mg/L, sensitivity of 81.5% and specificity of 84.1%, and for a PET score 3 and MRP values higher than 2.3 mcg/mL, sensitivity of 100% and specificity of 76.8%. In this study, we demonstrated that SAA and MRP can be useful as promising tools to detect GCA activity. The study demonstrates a good correlation between the two biomarkers and the imaging activity evaluated by the Halo and PET scores.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1154-1160"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107008","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}
Immunologic ResearchPub Date : 2024-10-01Epub Date: 2024-06-06DOI: 10.1007/s12026-024-09496-3
Irán Flores-Sotelo, Natalia Juárez, Marisol I González, Auraamellaly Chávez, Danielle T Vannan, Bertus Eksteen, Luis I Terrazas, José L Reyes
{"title":"Endogenous innate sensor NLRP3 is a key component in peritoneal macrophage dynamics required for cestode establishment.","authors":"Irán Flores-Sotelo, Natalia Juárez, Marisol I González, Auraamellaly Chávez, Danielle T Vannan, Bertus Eksteen, Luis I Terrazas, José L Reyes","doi":"10.1007/s12026-024-09496-3","DOIUrl":"10.1007/s12026-024-09496-3","url":null,"abstract":"<p><p>The NLRP3 receptor can assemble inflammasome platforms to trigger inflammatory responses; however, accumulating evidence suggests that it can also display anti-inflammatory properties. Here, we explored the role of nucleotide-binding oligomerization domain pyrin-containing protein 3 (NLRP3) in Taenia crassiceps experimental infection, which requires immune polarization into a Th2-type profile and peritoneal influx of suppressive macrophages for successful colonization. NLRP3 deficient mice (NLRP3<sup>-/-</sup>) were highly resistant against T. crassiceps, relative to wild-type (WT) mice. Resistance in NLRP3<sup>-/-</sup> mice was associated with a diminished IL-4 output, high levels of IL-15, growth factor for both innate and adaptive lymphocytes, and a dramatic decrease in peritoneum-infiltrating suppressive macrophages. Also, a transcriptional analysis on bone marrow-derived macrophages exposed to Taenia-secreted antigens and IL-4 revealed that NLRP3<sup>-/-</sup> macrophages express reduced transcripts of relm-α and PD-1 ligands, markers of alternative activation and suppressive ability, respectively. Finally, we found that the resistance displayed by NLRP3<sup>-/-</sup> mice is transferred through intestinal microbiota exchange, since WT mice co-housed with NLRP3<sup>-/-</sup> mice were significantly more resistant than WT animals preserving their native microbiota. Altogether, these data demonstrate that NLRP3 is a component of innate immunity required for T. crassiceps to establish, most likely contributing to macrophage recruitment, and controlling lymphocyte-stimulating cytokines such as IL-15.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"948-963"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261778","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":"Investigation of the relationship of tissue-resident γδ T cells and IL-17 gene expression with the pathogenesis of autoimmune hepatitis.","authors":"Nurullah Yucel, Gulam Hekimoglu, Sevinc Keser, Selma Erhan, Gamze Yesilay, Gulizar Hocaoglu, Muzaffer Seker","doi":"10.1007/s12026-024-09515-3","DOIUrl":"10.1007/s12026-024-09515-3","url":null,"abstract":"<p><p>Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease. Elevated serum immunoglobulin G (IgG) levels, autoantibodies, and histopathological interface hepatitis are the hallmarks of AIH. Autoantibodies and pathological findings, clinical and biochemical features, typical immunoglobulin levels, and exclusion of other diseases are used to diagnose the condition. Gamma-delta (γδ) T cells are a unique population of unconventional T cells with γ and δ glycoprotein chains. γδ T cells have been shown to play a crucial role in autoimmune diseases by producing interleukin (IL)-17. However, its role in AIH remains to be further elucidated. In this study, we aimed to examine the role of γδ T cells and IL-17 in the pathogenesis of AIH, by working on biopsy samples. Paraffin blocks of 18 patients with type 1 AIH and 18 control liver tissues were analyzed. qRT-PCR assessed IL-17 gene expression. Immunofluorescence double staining of CD3<sup>+</sup>TCRγδ<sup>+</sup> was performed to reveal tissue-resident γδ T cells' role in AIH. When comparing AIH to the control, there was a substantial increase in the ratio of CD3<sup>+</sup>TCRγδ<sup>+</sup> cells in total inflammatory cells (p = 0.01). IL-17 gene expression was lowered in AIH when compared to the control (p = 0.01). This study provides evidence for the involvement of γδ T cells and IL-17 in the pathogenesis of AIH. The ratio of γδ T cells and IL-17 gene expression showed a significant difference in AIH suggesting a potential role for γδ T cells in driving liver inflammation in A fIH.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"895-901"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633414","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}
Immunologic ResearchPub Date : 2024-10-01Epub Date: 2024-05-29DOI: 10.1007/s12026-024-09497-2
Lada Rumora, Ivona Markelić, Iva Hlapčić, Andrea Hulina Tomašković, Marija Fabijanec, Feđa Džubur, Miroslav Samaržija, Andrea Vukić Dugac
{"title":"Assessment of NLRP3 inflammasome activation in patients with chronic obstructive pulmonary disease before and after lung transplantation.","authors":"Lada Rumora, Ivona Markelić, Iva Hlapčić, Andrea Hulina Tomašković, Marija Fabijanec, Feđa Džubur, Miroslav Samaržija, Andrea Vukić Dugac","doi":"10.1007/s12026-024-09497-2","DOIUrl":"10.1007/s12026-024-09497-2","url":null,"abstract":"<p><p>The interplay between purinergic receptors as well as pattern recognition receptors like Toll-like receptors (TLRs) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) might have a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to determine and compare the concentrations of the damage-associated molecular patterns (DAMPs) heat shock protein 70 (Hsp70) and adenosine triphosphate (ATP), and gene expression of their respective receptors as well as NLRP3 inflammasome-related molecules in the peripheral blood of patients with end-stage COPD before and 1 year after lung transplantation (LT). Lung function was assessed by spirometry and diffusion capacity for carbon monoxide (DLCO). Quantitative polymerase chain reaction (qPCR) was applied for detection of TLR2, TLR4, P2X7R, P2Y2R, IL1B, CASP1, and NLRP3 expression. High-sensitivity ELISA kits were used for extracellular (e) Hsp70 and IL-1β, and luminescence assay for eATP measurements. Concentrations of eHsp70 and eATP as well as IL-1β were significantly increased in the plasma of end-stage COPD patients and significantly decreased after LT. In addition, TLR4, P2Y2R, IL1B, CASP1, and NLRP3 expression was up-regulated in COPD patients before LT, while it was significantly suppressed after LT. In conclusion, it could be assumed that NLRP3 inflammasome is activated in the peripheral blood of end-stage COPD patients and that eHsp70 and eATP could be responsible for its activation through triggering their receptors. On the other hand, previously enhanced pro-inflammatory reactions seem to be suppressed to the healthy population levels in lung recipients without allograft rejection.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"964-974"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175467","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}
Immunologic ResearchPub Date : 2024-10-01Epub Date: 2024-08-12DOI: 10.1007/s12026-024-09510-8
Jill R Schofield, Jill Brook, Denise Calaprice-Whitty
{"title":"Elevated total serum IgM predicts the presence of antiphospholipid antibodies in dysautonomia patients.","authors":"Jill R Schofield, Jill Brook, Denise Calaprice-Whitty","doi":"10.1007/s12026-024-09510-8","DOIUrl":"10.1007/s12026-024-09510-8","url":null,"abstract":"<p><p>Dysautonomia is an abnormal clinical state with multiple etiologies, including autoimmunity. Antiphospholipid antibodies (aPL) are among the autoantibodies that have been associated with autonomic dysfunction. We have observed that an elevated total serum IgM appears to be associated with the presence of aPL in dysautonomia patients. This is a retrospective study analyzing the clinical characteristics of 45 consecutive patients with cardiac autonomic dysfunction and a persistently elevated total serum IgM. 93% of patients were female with a mean age of 32.7 years. Most patients had severely disabling disease, with a mean Karnofsky-like functional ability score of 42% (normal 100%). 93% of patients tested persistently positive for one or more aPL and all patients tested persistently positive for aPL and/or Sjogren's antibodies. No patient had lupus specific antibodies. One third of patients experienced one or more thrombotic events and 58% of patients attempting pregnancy experienced pregnancy morbidity. Lastly, 78% of aPL-positive patients treated with antithrombotic therapy experienced 50 to 100% improvement in one or more symptoms (e.g., migraine, cognitive dysfunction) recognized to be responsive to antithrombotic therapy in a subset of aPL-positive patients and 73% of patients treated with and tolerating immune modulatory therapy experienced a positive response. We propose total serum IgM as a reliable and inexpensive test that can be used to identify dysautonomia patients at risk for persistent aPL-positivity. These patients are important to identify as they have a significant risk for thrombosis and pregnancy morbidity and often experience significant symptomatic improvement with antithrombotic therapy and/or immune modulatory therapy.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1086-1091"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971038","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}
Immunologic ResearchPub Date : 2024-10-01Epub Date: 2024-07-03DOI: 10.1007/s12026-024-09500-w
Judith W Heutz, Agnes E M Looijen, Jac H S A M Kuijpers, Marco W J Schreurs, Annette H M van der Helm-van Mil, Pascal H P de Jong
{"title":"The prognostic value of IgA anti-citrullinated protein antibodies and rheumatoid factor in an early arthritis population with a treat-to-target approach.","authors":"Judith W Heutz, Agnes E M Looijen, Jac H S A M Kuijpers, Marco W J Schreurs, Annette H M van der Helm-van Mil, Pascal H P de Jong","doi":"10.1007/s12026-024-09500-w","DOIUrl":"10.1007/s12026-024-09500-w","url":null,"abstract":"<p><p>The mucosal origin hypothesis of rheumatoid arthritis has renewed the interest in IgA autoantibodies, but their added value over IgG anti-citrullinated protein antibody (ACPA) and IgM rheumatoid factor (RF) for modern treatment outcomes remains unknown. We aimed to investigate the prognostic value of IgA-ACPA and IgA-RF for treatment outcomes in an early arthritis population. IgA-ACPA/RF isotypes were measured in baseline sera from 480 inflammatory arthritis (IA) patients, who were included in the treatment in the Rotterdam Early Arthritis Cohort trial (tREACH). The tREACH trial was a multicentre, stratified, single-blinded trial with a treat-to-target approach. The prognostic value of IgA-ACPA/RF was determined by evaluating differences in (1) quick-attained (< 6 months after diagnosis) and persistent remission rates, (2) DMARD-free remission and (3) biological use between IA patients with and without IgA-ACPA/RF over 3 years of follow-up. IgA-ACPA was present in 23% of patients and overlapped with IgG-ACPA positivity in 94%. Similarly, IgA-RF overlapped with IgM-RF in 90% of patients. IgA-ACPA positivity was associated with lower DFR rates and more biological use, but this effect was largely mediated by the presence of IgG-ACPA, since this effect disappeared after stratification for IgG-ACPA (HR 0.6, 95%CI 0.2-1.6 for DFR). No differences were observed in 'quick-attained and persistent remission' rates and for IgA-RF. Their seems to be no additional value of IgA-ACPA and IgA-RF for modern, long-term clinical outcomes. The effects of IgA-ACPA seen in our study are largely mediated by the presence of IgG-ACPA. Based on these results, there is no rationale for measuring these isotypes in daily practice.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"982-990"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497926","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}
Immunologic ResearchPub Date : 2024-10-01Epub Date: 2024-07-17DOI: 10.1007/s12026-024-09517-1
Rabab El Hawary, Safa Meshaal, Sohilla Lotfy, Dalia Abd Elaziz, Alia S Eldash, Aya Erfan, Radwa Alkady, Rania Darwish, Mai Saad, Engy Chohayeb, Nermeen Galal, Aisha M Elmarsafy
{"title":"A novel MALT1 variant in an Egyptian patient presenting with exfoliative dermatitis: a case-based review.","authors":"Rabab El Hawary, Safa Meshaal, Sohilla Lotfy, Dalia Abd Elaziz, Alia S Eldash, Aya Erfan, Radwa Alkady, Rania Darwish, Mai Saad, Engy Chohayeb, Nermeen Galal, Aisha M Elmarsafy","doi":"10.1007/s12026-024-09517-1","DOIUrl":"10.1007/s12026-024-09517-1","url":null,"abstract":"<p><p>Inborn errors of the CARD11-BCL10-MALT1 (CBM) signalosome have recently been shown to underlie severe combined immunodeficiency (SCID) and combined immunodeficiency (CID) with variable immunological and clinical phenotypes, and patients usually present with recurrent bacterial, viral, and fungal infections, periodontal disease, enteropathy, dermatitis, and failure to thrive. In the present study, we describe the clinical and immunological characteristics of an Egyptian patient with a mutation in the MALT1 gene. The patient suffered from an itchy exfoliative skin rash and eczematous lesions over his face and flexural surface of the limbs. He also had dental enamel erosion, repeated attacks of diarrhea, and pneumonia. He had elevated serum IgE and normal B- and T-lymphocyte subset counts, but there was an arrest in the B-cell maturation. DOCK8 expression on the lymphocytes by flow cytometry was normal. Next-generation sequencing revealed a novel homozygous variant in the MALT1 gene (c.762dup in exon 5 of 17; p.Ile255TyrfsTer10); this variant is likely pathogenic, thus supporting the genetic diagnosis of immunodeficiency-12 (IMD12). Although the presence of eczema, recurrent sinopulmonary, and staphylococcal infections are suggestive of DOCK8 deficiency, they are also a finding in CARD11 and MALT1 deficiency. Thus, whenever DOCK 8 has been excluded, the molecular diagnosis is mandatory as this could lead to discovering more patients hence better understanding and reporting of the phenotype and natural history of the disease especially since there are very few documented cases. Early diagnosis will also enable the proper patient management by hematopoietic stem cell transplantation (HSCT) prior to the establishment of infections and pulmonary damage leading to a better outcome.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1147-1153"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626661","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}
Xiaoyu Liu, Yan Li, Weijian Zhang, Nan Gao, Jie Chen, Cheng Xiao, Guoqiang Zhang
{"title":"Correction: Inhibition of cIAP1/2 reduces RIPK1 phosphorylation in pulmonary endothelial cells and alleviate sepsis-induced lung injury and inflammatory response.","authors":"Xiaoyu Liu, Yan Li, Weijian Zhang, Nan Gao, Jie Chen, Cheng Xiao, Guoqiang Zhang","doi":"10.1007/s12026-024-09502-8","DOIUrl":"10.1007/s12026-024-09502-8","url":null,"abstract":"","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1198"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199834","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}
Immunologic ResearchPub Date : 2024-10-01Epub Date: 2024-05-29DOI: 10.1007/s12026-024-09498-1
Gamze Kılıç, Kemal Faruk Körüklü, Muhammed Galip Kumcu, Elif Çakır, Murat Karkucak, Erkan Kılıç
{"title":"Gender disparities in Behçet's syndrome: identifying distinct phenotypes through cluster analysis.","authors":"Gamze Kılıç, Kemal Faruk Körüklü, Muhammed Galip Kumcu, Elif Çakır, Murat Karkucak, Erkan Kılıç","doi":"10.1007/s12026-024-09498-1","DOIUrl":"10.1007/s12026-024-09498-1","url":null,"abstract":"<p><p>Behçet's syndrome (BS) is a complex, multi-systemic disorder with a global occurrence, notably concentrated along the Silk Road. This study aimed to investigate gender-specific expressions and clinical phenotypes in BS patients within the Eastern Black Sea Region of Turkey. A total of 290 BS patients were retrospectively analyzed between January 2013 and December 2023. Demographic characteristics, clinical manifestations, medical treatment, and pathergy test results were obtained from a review of medical records. The mean age was 45.79 ± 13.05, with a male-to-female ratio of 48.6:51.4. Male patients had higher papulopustular lesions (p < 0.001) and ocular involvement (p = 0.036), while females showed more frequent genital ulcers (p = 0.032). Medication usage showed gender-based variations, notably higher corticosteroid, azathioprine, and tumor necrosis factor-alpha inhibitor (TNFi) use in males (p < 0.001). Cluster analysis revealed five distinct clusters, each with unique features and gender predominance. Cardiovascular type, ocular type, and skin type predominantly featured male patients, while joint involvement type and neurologic and mucosal involvement type were more prevalent among female patients with BS. This research contributes valuable insights into the gender-related clinical variations of BS within a specific geographic region, fostering a more comprehensive understanding of this challenging syndrome. The identification of distinct clinical phenotypes facilitates the development of tailored treatment strategies, potentially leading to improved outcomes for patients with BS.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"975-981"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160899","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":"DNA demethylase Tet2 promotes the terminal maturation of natural killer cells.","authors":"Yuqing Lin, Biyun Yang, Hailin Liu, Guanghe Ran, Liang Song, Meng Meng, Xiaofeng Yin, Qinghua Bi, Dongmei Yan, Youcai Deng, Yonghui Lu","doi":"10.1007/s12026-024-09506-4","DOIUrl":"10.1007/s12026-024-09506-4","url":null,"abstract":"<p><p>The cytotoxicity feature to eliminate malignant cells makes natural killer (NK) cells a candidate for tumor immunotherapy. However, this scenario is currently hampered by inadequate understanding of the regulatory mechanisms of NK cell development. Ten-Eleven-Translocation 2 (Tet2) is a demethylase whose mutation was recently shown to cause phenotypic defects in NK cells. However, the role of Tet2 in the development and maturation of NK cells is not entirely clear. Here we studied the modulatory role of Tet2 in NK cell development and maturation by generating hematopoietic Tet2 knockout mice and mice with Tet2 conditional deletion in NKp46<sup>+</sup> NK cells. The results showed that both hematopoietic and NK cell conditional deletion of Tet2 had no effect on the early steps of NK cell development, but impaired the terminal maturation of NK cells defined by CD11b, CD43, and KLRG1 expression. In the liver, Tet2 deletion not only prevented the terminal maturation of NK cells, but also increased the proportion of type 1 innate lymphoid cells (ILC1s) and reduced the proportion of conventional NK cells (cNK). Moreover, hematopoietic deletion of Tet2 lowered the protein levels of perforin in NK cells. Furthermore, hematopoietic deletion of Tet2 downregulated the protein levels of Eomesodermin (Eomes), but not T-bet, in NK cells. In conclusion, our results demonstrate that Tet2 plays an important role in the terminal maturation of NK cells, and the Eomes transcription factor may be involved.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"908-920"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310620","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}