Immunologic Research最新文献

{"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":"https://doi.org/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":"","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":"","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":"https://doi.org/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":"https://doi.org/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}

{"title":"Immunomodulatory effects of medicinal leech saliva extract on in vitro activated macrophages.","authors":"Hüseyin Ayhan, Sedat Sevin, Seyhan Karaaslan, Furkan Ayaz","doi":"10.1007/s12026-024-09575-5","DOIUrl":"https://doi.org/10.1007/s12026-024-09575-5","url":null,"abstract":"<p><p>Leech therapy has been utilized in modern and traditional medicine. Leech saliva contains versatile peptides and molecules that can exert anti-microbial, anti-inflammatory, anti-coagulant, and analgesic activities on the patients. The active components and molecular mechanism of action of these components should be deciphered properly in order to generate biotechnological drug candidates by recombinant production of the leech saliva peptides. In our study, we conducted LC-MS/MS and proteomics analysis on the lyophilized leech saliva extract to determine the components of it. Moreover, this extract was tested on the in vitro-activated macrophages. The extract decreased the production of the pro-inflammatory cytokines by the activated mammalian macrophages compared to the positive control groups. These results suggest that the lyophilized leech saliva can be utilized as an anti-inflammatory biotechnological drug candidate against inflammatory and autoimmune disorders. In vitro studies will be conducted to further decipher the most active ingredients in the leech saliva. These active components will be tested on the animal models of the inflammatory and autoimmune disorders to show their drug potential.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"9"},"PeriodicalIF":3.3,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817976","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":"Clinical and molecular profile of 20 patients with DOCK8 deficiency-a single-center experience from Southern India.","authors":"Neha Singh, Priya Ranganath, Ananthvikas Jayaram, Prerna Jhawar, Udhaya Kotecha, Jyothi Janardhanan, Harish Kumar, K A Sudheer, Syed Mohammed Naushad Ali, Karthik Arigela, Chetan Ginigeri, Sagar Bhattad","doi":"10.1007/s12026-024-09571-9","DOIUrl":"https://doi.org/10.1007/s12026-024-09571-9","url":null,"abstract":"<p><p>DOCK8 deficiency is the most common cause of autosomal recessive hyper-IgE syndrome (AR-HIES). The clinical spectrum is wide resulting in combined immunodeficiency, atopy, autoimmunity, and malignancies. To study the clinical and molecular profile of 20 patients with DOCK8 deficiency. Four hundred and eight patients with various inborn errors of immunity (IEIs) were diagnosed in the Pediatric Immunology Unit of our hospital during the study period of February 2017 to August 2023. Based on the clinical and immunological phenotype, DOCK8 deficiency was suspected in 31 patients. Genetic studies confirmed DOCK8 deficiency in 20 patients, and their profile was analyzed in detail. Twenty patients from 17 kindreds were diagnosed with DOCK8 deficiency. The female-to-male ratio was 1.2:1. The mean age at onset of symptoms and diagnosis was 9.8 and 69.8 months, respectively. Thirteen out of 17 families (76%) reported consanguinity. Eczema was the presenting manifestation in 19 patients (95%). Mucocutaneous manifestations included oromucosal hyperpigmentation (n = 8), scalp seborrhoea (n = 2), psoriasis (n = 2), and alopecia (n = 1). The spectrum of infections included pneumonia (n = 14), otitis media (n = 6), gastrointestinal infections (n = 6), cutaneous viral infections (n = 5), oral candidiasis (n = 4), and meningoencephalitis (n = 2). Three patients had developed bronchiectasis. Four patients had autoimmune manifestations including autoimmune hemolytic anemia (n = 2) and vasculitis (n = 2). The whole exome sequencing showed deletions (8 kindreds) as the most common mutation in the DOCK8 gene. Overall, 11 of these mutations were novel. Ten patients were on monthly intravenous immunoglobulin therapy and antibiotic prophylaxis at the time of writing this paper. Three patients underwent hematopoietic stem cell transplants elsewhere, two of whom succumbed to post-transplant complications and one is doing well. Nine patients died during the study period. We present one of the largest single-center experiences on DOCK8 deficiency from India. A significant delay in the diagnosis contributed to poor outcomes in our cohort.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"8"},"PeriodicalIF":3.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813205","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":"OGT promotes the ferroptosis of chondrocytes in osteoarthritis development via O-GlcNAcylation modification of ACSF2.","authors":"Yin Zhang, Zongrui Qiao, Mang He, Junfeng Xia","doi":"10.1007/s12026-024-09567-5","DOIUrl":"https://doi.org/10.1007/s12026-024-09567-5","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a chronic degenerative joint disease that imposes a substantial economic burden on patients and society. The aim of this study was to investigate the effects of O-linked N-acetylglucosamine transferase (OGT) and OGT-mediated O-GlcNAcylation on cartilage injury and chondrocyte ferroptosis in OA. An OA model was established using mice for the in vivo study. Lipopolysaccharide (LPS)-induced chondrocytes were used as a cell model for the in vitro study. RNA and protein expressions were detected using RT-qPCR and Western blotting, respectively. Co-immunoprecipitation (Co-IP) was performed to investigate protein-protein interactions. Lipid reactive oxygen species (ROS) were detected via flow cytometry. Levels of Fe²⁺, glutathione (GSH), lipid peroxidation products (LPO), and malondialdehyde (MDA) were assessed using commercial kits. Cell proliferation and death were evaluated using CCK-8 assays and propidium iodide (PI) staining, respectively. The results indicated that total O-GlcNAcylation and OGT levels were increased in OA models. Inhibition and silencing of OGT suppressed LPS-induced chondrocyte injury. OGT mediated the O-GlcNAcylation of Acyl-CoA Synthetase Family Member 2 (ACSF2), enhancing its stability. O-GlcNAcylation at serine 385 (S385) of ACSF2 mediated its effect on promoting ferroptosis. Additionally, conditional knockout of OGT alleviated OA injury in mice. We demonstrated that OGT mediates OA progression both in vitro and in vivo. Mechanistically, OGT-induced O-GlcNAcylation of ACSF2 at S385 mediates chondrocyte ferroptosis.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"7"},"PeriodicalIF":3.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813206","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":"Regnase-1 regulates inflammation in T cells of ankylosing spondylitis through the TRAF6.","authors":"Yuxin Ren, Yujie Deng, Ziqi Li, Yanyu Zhao, Hanqing Wu, Longbao Xu, Guoqing Li, Hui Zhao, Mengmeng Wang, Guoqi Cai, Faming Pan","doi":"10.1007/s12026-024-09555-9","DOIUrl":"https://doi.org/10.1007/s12026-024-09555-9","url":null,"abstract":"<p><p>The study aimed to investigate the regulatory role of Regnase-1 in ankylosing spondylitis (AS) inflammation. We collected 10 ml peripheral venous blood and epidemiological data from 45 AS patients and 45 healthy controls and performed enzyme-linked immunosorbent assay (ELISA) experiments to measure the levels of inflammatory cytokines. Then CD3 + T lymphocytes were isolated by magnetic bead sorting method, and the transcriptional levels of Regnase-1 and TNF receptor-associated factor 6 (TRAF6) were detected by real-time quantitative PCR (qRT-PCR). The regnase-1 knockdown human T lymphocyte leukemia cell (Jurkat T) model was constructed by small interfering RNA (siRNA) technology. Then PCR and Western blot were used to detect the transcription level and protein level of downstream genes. Co-immunoprecipitation was used to verify the interaction between Regnase-1 and TRAF6. Regnase-1 and TRAF6 transcription levels were down-regulated and positively correlated with each other in T cells from AS patients. The ROC curve analysis indicates that both Regnase-1 and TRAF6 possess diagnostic capabilities, with Regnase-1 demonstrating a particularly high area under the curve (AUC) of 0.876 (95% CI: 0.789-0.936). Subgroup analysis shows NSAIDs boost Regnase-1 and TRAF6 transcription while reducing IL23 and IL17 levels. The results of cell experiments showed that si-Regnase-1 significantly reduced the mRNA and protein levels of TRAF6 in Jurkat T cells and increased the expression level of inflammatory gene TNF-α. Co-immunoprecipitation assay further verified the binding between the two proteins. Regnase-1 may participate in the chronic inflammatory process of AS by regulating TNF-α through TRAF6.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"5"},"PeriodicalIF":3.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806928","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":"Arginine vasopressin (AVP) treatment increases the expression of inhibitory immune checkpoint molecules in monocyte-derived dendritic cells.","authors":"Zahra Ghahramanipour, Bahar Naseri, Amirhossein Mardi, Sepideh Sohrabi, Javad Masoumi, Elham Baghbani, Hadi Karimzadeh, Behzad Baradaran","doi":"10.1007/s12026-024-09579-1","DOIUrl":"https://doi.org/10.1007/s12026-024-09579-1","url":null,"abstract":"<p><p>Arginine vasopressin (AVP) has disparate impacts on immune responses by divergent receptors on cells including DCs. This study was conducted with the aim of investigating the impact of AVP on the maturation and expression of the inhibitory immune checkpoint molecules in tolerogenic monocyte-derived DCs. CD14 marker was used to separate monocytes from peripheral blood mononuclear cells (PBMCs) by MACS method. To differentiate monocytes from DCs, we utilized GM-CSF and IL-4 cytokines. Tolerogenic DCs were generated using vitamin D3 and dexamethasone. We added LPS and AVP to the culture medium on day 6 after incubation of DCs at 37 °C. Finally, we assessed the surface molecules by flow cytometry and used real-time PCR to evaluate the expression of genes related to the inhibitory immune checkpoints. Based on the obtained data, AVP increased the expression of CD11c (P ≤ 0.0001), HLA-DR (P ≤ 0.01), and CD86 (P ≤ 0.01) in AVP-mDCs. Also, the expression of all the immune checkpoint genes including CTLA-4 (P ≤ 0.001), BTLA (P ≤ 0.001), PDL-1 (P ≤ 0.05), B7H7 (P ≤ 0.001), LAG3 (P ≤ 0.01), and VISTA (P ≤ 0.001) in AVP-mDCs was increased in comparison to the control group. Vasopressin caused the generation of mature and tolerogenic DCs. Our data may help to consider AVP-mDCs to take part in autoimmune disease therapy, transplanted tissue rejection impedance, and allergies.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"6"},"PeriodicalIF":3.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806922","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":"The function of CD8 + T cells in the absence of MHC-I in target cells: what to learn from the deficiency of MHC-I expression in humans.","authors":"Rafael Cardoso Maciel Costa Silva","doi":"10.1007/s12026-024-09556-8","DOIUrl":"https://doi.org/10.1007/s12026-024-09556-8","url":null,"abstract":"","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"4"},"PeriodicalIF":3.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806934","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":"Sustainability, intelligence, and more immunology: time to get back to the future!","authors":"Sakir Ahmed","doi":"10.1007/s12026-024-09554-w","DOIUrl":"10.1007/s12026-024-09554-w","url":null,"abstract":"","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"3"},"PeriodicalIF":3.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806931","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}