Clinical and experimental immunology最新文献

{"title":"The role of vitamin D: a promising pathway to combat neuropsychiatric lupus disorders.","authors":"Thaís Evelyn Karnopp, Gustavo Flores Chapacais, Maria Luísa Gasparini, Natália Garcia Dos Santos, Vinicius da Silva Freitas, Marina Piccoli, Andressa Leite Di Domenico, Lucas Denardi Doria, Nikolas Mateus Pereira de Souza, Alexandre Rieger, Eduarda Correa Freitas, Fernanda Visioli, Odirlei André Monticielo","doi":"10.1093/cei/uxae099","DOIUrl":"10.1093/cei/uxae099","url":null,"abstract":"<p><p>To evaluate neuropsychiatric manifestations in the pristane-induced lupus (PIL) model, as well as to evaluate immunoregulatory effects of vitamin D (vit-D) in the brain of mice with PIL. Eighty female BALB/c mice were divided into six groups with 90 (3 months) and 180 (6 months) days of experimentation: CO3, CO6 (controls), PIL3, PIL6 (pristane-induced lupus), VD3 and VD6 (PIL supplemented with 1,25-dihydroxyvitamin D). Forced-swim, elevated plus maze and Barnes maze were the behavioral tests performed. Expression of pVDR was assessed by immunofluorescence. Brain IgM and IgG deposits were evaluated by double staining fluorescence. Serum IL-6 and IFN-α1 were quantified by ELISA. AUC-ROC curve was also performed for immunoglobulins. PIL and VD showed depressive-like behavior in the forced-swim test and anxious-like behavior in the elevated plus maze test. PIL also presented cognitive and memory impairment in the Barnes maze test. Additionally, PIL and VD presented higher levels of serum IFN-α1, but not IL-6. Mice supplemented with vit-D had reduced IgM and IgG deposits and increased pVDR expression in the brain after 180 days. The AUC-ROC curve demonstrated high sensitivity and specificity for IgM and IgG in the brain. We observed neuropsychiatric manifestations in this model of systemic lupus erythematosus (SLE), strongly corroborating to PIL model being suitable as a neuropsychiatric lupus (NPSLE) model. Vit-D was able to reduce immunoglobulin deposits in the brain and influenced the levels of serum IL-6 in the animals assessed. Also, it improved memory, but it had no effect on depressive and anxious-like behavior.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic accuracy of saliva-based testing as a Vibrio cholerae surveillance tool among naturally infected patients.","authors":"Caroline C Chisenga, Bernard Phiri, Harriet Ng'ombe, Mutinta Muchimba, Fraser Liswaniso, Biana Bernshtein, Adam F Cunningham, David Sack, Samuel Bosomprah","doi":"10.1093/cei/uxae092","DOIUrl":"10.1093/cei/uxae092","url":null,"abstract":"<p><p>Saliva, as a diagnostic medium, offers a promising alternative to blood by virtue of its non-invasive collection, which enhances patient compliance, especially in paediatric and geriatric populations. In this study, we assessed the utility of saliva as a non-invasive medium for measuring Vibrio cholerae-specific serum antibodies in naturally infected individuals. We tested paired serum and saliva samples obtained from a total of 63 patients with cholera enrolled in a cohort study. Vibriocidal antibodies assay (IgM/IgG) as markers for accurate determination was used to determine cholera-specific antibody levels. Using receiver operating characteristics (ROC) curve, we found that the best cut-off that maximizes (sensitivity + specificity) is 10 titres. At this saliva titre, the sensitivity is 76.9% (95%CI: 60.9%, 87.7%) and specificity is 80.0% (95%CI: 56.6%, 92.5%). Using Spearman's correlation coefficient, we also found evidence of a positive correlation between V. cholerae saliva and serum antibodies (rho = 0.66, P < 0.001). In conclusion, saliva-based diagnostic cholera tests have high diagnostic accuracy and would be advantageous, cheaper, and quicker for early diagnosis of severe cholera outcomes.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antigen-specific T-cell frequency and phenotype mirrors disease activity in DRB1*04:04+ rheumatoid arthritis patients.","authors":"Cliff Rims, Hannes Uchtenhagen, Kadin Brooks, Bernard Ng, Sylvia E Posso, Jeffrey Carlin, William W Kwok, Jane H Buckner, Eddie A James","doi":"10.1093/cei/uxae102","DOIUrl":"10.1093/cei/uxae102","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is associated with high-risk HLA class II alleles known as the \"RA shared epitope.\" Among prevalent shared epitope alleles, study of DRB1*04:04 has been limited. To define relevant epitopes, we identified citrullinated peptide sequences from synovial antigens that were predicted to bind to HLA-DRB1*04:04 and utilized a systematic approach to confirm their binding and assess their recognition by CD4 T cells. After confirming the immunogenicity of 13 peptides derived from aggrecan, cartilage intermediate layer protein (CILP), α-enolase, vimentin, and fibrinogen, we assessed their recognition by T cells from a synovial tissue sample, observing measurable responses to 8 of the 13 peptides. We then implemented a multicolor tetramer panel to evaluate the frequency and phenotype of antigen-specific CD4 T cells in individuals with anti-citrullinated protein antibody-positive RA and controls. In subjects with RA, CILP-specific T-cell frequencies were significantly higher than those of other antigens. The surface phenotypes exhibited by antigen-specific T cells were heterogeneous, but Th1-like and Th2-like cells predominated. Stratifying based on disease status and activity, antigen-specific T cells were more frequent and most strongly polarized in RA subjects with high disease activity. In total, these findings identify novel citrullinated epitopes that can be used to interrogate antigen-specific CD4 T cells and show that antigen-specific T-cell frequency is elevated in subjects with high disease activity.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to letter to the editor: tubulin beta is not the target of antineutrophil antibodies in primary sclerosing cholangitis.","authors":"Beate Preuß, Reinhild Klein","doi":"10.1093/cei/uxae064","DOIUrl":"10.1093/cei/uxae064","url":null,"abstract":"","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental induction of anti-muscarinic type-3-receptor extracellular loop antibodies by immunization with 4-hydroxy-2-nonenal modified Ro60 and unmodified Ro60.","authors":"Biji T Kurien, Devavrat Dave, Martha Tsaliki, Syed M S Quadri, Valerie M Lewis, Robert Hal Scofield","doi":"10.1093/cei/uxae114","DOIUrl":"10.1093/cei/uxae114","url":null,"abstract":"<p><strong>Objective: </strong>Sjögren's Disease (SjD) subjects have decreased lacrimal/salivary gland function. Studies have proposed that autoantibodies targeting G-protein-coupled muscarinic acetylcholine-type-3-receptor (M3R) are potential clinical markers for SjD. We hypothesized that rabbits/mice immunized with 4-hydroxy-2-nonenal (HNE)-modified/unmodified Ro60 will develop an autoimmunity, specifically a SjD phenotype, thus expressing increased levels of anti-M3R antibodies.</p><p><strong>Methods: </strong>We immunized two rabbits each with 10 mM HNE-modified Ro60/unmodified Ro60 antigen or Ro274-290/Ro413-428/Ro500-517 Ro60 peptides. Two rabbits each were immunized with either M3R second extracellular loop (ECL2) or M3R ECL3 peptide. Finally, five groups of BALB/c mice were immunized as follows-Group-I immunized with Ro60, Groups-II-IV immunized with Ro60 modified with 0.4 mM (low), 2 mM (medium), and 10 mM (high) HNE, respectively and Group-V-Freund's adjuvant. Serum antibodies to M3R ECL2/ECL3/Ro60/La or Sm were detected by ELISA. Functional assays were also performed.</p><p><strong>Results: </strong>Immunization with HNE-modified Ro60/unmodified Ro60 antigen or Ro274/Ro 413/Ro500 peptides induced a rapid intermolecular epitope spreading to M3R ECL2/ECL3, especially to M3R ECL3 in HNE-Ro immunized rabbits. These animals did not bind to scrambled M3R peptides. Ro60-immunized rabbit IgG inhibited M3R activity in a functional assay. Rabbits immunized with ECL2/ECL3 developed high reactivity to Ro60 but not against Sm/RNP. We found a differential antibody-induction against M3R ECL2 with Group-3 mice developing significant reactivity.</p><p><strong>Conclusion: </strong>Our data show induction of increasing anti-M3R antibodies in rabbits immunized with Ro60/HNE-Ro60 or Ro60 peptides and differential induction of these antibodies in mice immunized with Ro60 modified with increasing HNE. These findings suggest that M3R ECL2/ECL3 are involved in SjD autoimmunity progression.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and Phase 1 study of a novel monoclonal antibody against human IL-1β for the treatment of IL-1β-mediated diseases.","authors":"Minseon Cho, Susan H Tam, Lihua Shi, Isa Fung, Mark Tornetta, Gabriela A Canziani, Man-Cheong Fung, Mark L Chiu, Chao Han, Di Zhang","doi":"10.1093/cei/uxaf009","DOIUrl":"10.1093/cei/uxaf009","url":null,"abstract":"<p><p>Interleukin-1β (IL-1β) is a key mediator of innate immunity against pathogen infections. However, dysregulated IL-1β activity is associated with various autoinflammatory, autoimmune, degenerative, atherosclerotic diseases, and cancers. Biologic drugs that neutralize excess IL-1β activity, such as canakinumab, have been effective in treating IL-1β-mediated diseases. This article reports the discovery and development of a novel humanized anti-IL-1β antibody, designated as TAVO103A, which exhibited potent binding affinities to human and monkey IL-1β. TAVO103A demonstrated more potent neutralization of IL-1β activities compared to canakinumab in multiple assays, including tests on the IL-1β-driven signal transduction cascade, inflammatory cytokine release from MRC-5 cells, chemokine release from A549 cells, and the proliferation of D10.G4.1 helper T cells. Ex vivo studies showed that TAVO103A effectively neutralized IL-1β-mediated release of pro-inflammatory cytokines from peripheral blood mononuclear cells. In addition, TAVO103A exhibited dose-dependent efficacy in a knee joint inflammation mouse model. TAVO103A underwent Fc engineering to reduce binding to Fcγ receptors, increase affinity to FcRn receptors, and enhance its resistance to proteolytic degradation. In a Phase 1 study, TAVO103A was found to be safe, well tolerated, and demonstrated a median half-life of 63 days in healthy subjects. By recognizing a different epitope, TAVO103A provided more potent neutralization of IL-1β activities, a longer circulating half-life, and improved safety profiles compared to canakinumab, positioning it to be a potential best-in-class therapeutic option for various IL-1β-mediated diseases.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engaging PD-1 rescuesregulatory T cell function and inhibits inflammatory T cells in rheumatoid arthritis.","authors":"Kaustav Chowdhury, Uma Kumar, Jaydeep Chaudhuri, Prabin Kumar, Soumabha Das, Maumita Kanjilal, Parasar Ghosh, Ravi Kiran Basyal, Uma Kanga, Santu Bandyopadhaya, Dipendra Kumar Mitra","doi":"10.1093/cei/uxaf035","DOIUrl":"10.1093/cei/uxaf035","url":null,"abstract":"<p><strong>Background: </strong>Despite their synovial enrichment, regulatory T cells (Treg) fail to alleviate the joint inflammation in rheumatoid arthritis (RA). This indicates their functional impairment in the synovial milieu of RA patients.</p><p><strong>Results: </strong>Here, we demonstrate that a deficit in the PD-1 pathway incapacitates the synovial Treg cells, and engaging programmed cell death protein-1 (PD-1) restores their suppressive function (interleukin 10, transforming growth factor beta secretion), which in turn suppresses the synovial inflammatory T cells (IFN-γ+, IL-17+ TNF-α+). We also showed that a deficit in programmed death ligand-1 expression on RA synovial macrophages contributes to impaired Treg cell function.</p><p><strong>Conclusion: </strong>Rejuvenating synovial Treg cell function via PD-1 engagement may be a potential strategy to ameliorate the synovial inflammation in RA patients.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1-methyl-tryptophan improves anxiety-like behavior in colitis mice by inhibiting neuroinflammation, promoting cell regeneration, and decreasing apoptosis.","authors":"Li-Ping Zhao, Lu-Lu Tan, Yi-Meng Xia, Xiao-Yu Ma, Ting Li, Sheng-Yang Zhou, Jian Wu, Ming-An Li, Wei-Jiang Zhao, Yan-Qin Shen","doi":"10.1093/cei/uxaf030","DOIUrl":"10.1093/cei/uxaf030","url":null,"abstract":"<p><strong>Introduction: </strong>Mood disorders such as anxiety are important extraintestinal manifestations of inflammatory bowel disease (IBD) and are more prevalent in active IBD. Studies have shown that pharmacologically induced anxiety was correlated with changes in plasma Kynurenine (Kyn) concentrations. Our previous study also found that Kyn was abnormally increased in the serum and brain of mice with acute colitis. This study aimed to investigate the role and possible mechanism of Kyn in anxiety-like behavior induced by colitis.</p><p><strong>Methods: </strong>Therefore, we established a 3% dextran sulfate sodium-induced mouse model of acute colitis. Kyn is produced by tryptophan metabolism in the presence of indoleamine 2,3-dioxygenase (IDO, rate-limiting enzyme). Furthermore, 1-methyl-tryptophan (1-MT), as an IDO inhibitor, was used to reduce Kyn synthesis in this study.</p><p><strong>Results: </strong>We found that 1-MT significantly improved anxiety-like behaviors in mice with colitis, as assessed by the marbles burying test. Moreover, our study demonstrated that 1-MT reduced the level of pro-inflammatory cytokine IL-1β and the activation of glial cells in the mouse brain, indicating the anti-inflammatory effect of 1-MT. Similarly, 1-MT inhibited lipopolysaccharide-induced inflammatory responses in BV2 cells, which was consistent with the in vivo results. Furthermore, 1-MT reversed the low expression of doublecortin (DCX) and proliferating cell nuclear antigen (PCNA) in the hippocampus caused by colitis, suggesting a pro-neurogenesis and pro-proliferation effect. In addition, we found that Kyn promoted apoptosis by regulating the Bax/Bcl2 signaling cascade through in vitro and in vivo experiments.</p><p><strong>Conclusion: </strong>Overall, these results suggest that 1-MT improved anxiety-like behaviors in mice with colitis by decreasing neuroinflammation, promoting neurogenesis and cell proliferation, and reducing apoptosis.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intratumoral injection of R848 and poly(I:C) synergistically promoted antitumor immune responses by reprogramming macrophage polarization and activating DCs in lung cancer.","authors":"Shuanghui Chen, Linzhao Li, Haohua Yuan, Huan Gui, Quan Wan, Mengjiao Wang, Hang Lv, Chenglv Wang, Lan Zhu, Yingjie Nie, Xiangyan Zhang","doi":"10.1093/cei/uxae110","DOIUrl":"10.1093/cei/uxae110","url":null,"abstract":"<p><strong>Introduction: </strong>Immunotherapy has rapidly become a primary treatment option for many lung cancer patients because of its success in treating this prevalent and deadly disease. However, the success of immunotherapy relies on overcoming the immunosuppressive tumor microenvironment, making remodeling this environment a potential strategy for lung cancer therapy. Research suggests that Toll-like receptor (TLR) agonists can impede tumor growth by promoting the conversion of tumor-associated macrophages into an M1-like state or enhancing dendritic cell development. However, there is insufficient research on the combined use of TLR agonists for treating lung cancer.</p><p><strong>Methods: </strong>In this study, we examined how TLR agonists such as resiquimod (R848) and poly(I:C) impact lung cancer treatment when used alone or in combination. In vitro, the regulatory functions and mechanisms of R848 and poly(I:C) were analyzed in primary macrophages, RAW264.7 cells, and primary dendritic cells (DCs). Tumor treatment efficacy was assessed in vivo with a Lewis lung carcinoma (LLC) mouse model.</p><p><strong>Results: </strong>The combination of R848 + poly(I:C) enhances the transformation of macrophages from the M2 phenotype to the M1 phenotype by increasing inflammatory cytokine levels. The percentage of mature DCs expressing MHC-II+CD11c+ and CD86+ cells was significantly higher in the R848 + poly(I:C) group compared with the other groups. Intratumoral injection of the synergistic combination of R848 + poly(I:C) suppressed tumor growth by increasing the M1:M2 ratio in TAMs, activating DCs, and attracting CD4+ and CD8+ T cells.</p><p><strong>Conclusion: </strong>R848 + poly(I:C) synergistically induces M1-like polarization of macrophages, activates DCs, and promotes effective antitumor immunity in mice with subcutaneous LLC tumors.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nck1 regulates the in vitro development of human regulatory T cells through AKT pathway.","authors":"Aussanee Nuiyen, Donruedee Sanguansermsri, Jarun Sayasathid, Kanthachat Thatsakorn, Siraphop Thapmongkol, Jatuporn Ngoenkam, Sutatip Pongcharoen","doi":"10.1093/cei/uxaf011","DOIUrl":"10.1093/cei/uxaf011","url":null,"abstract":"<p><p>T cell receptor (TCR) signalling is crucial in determining the fate of thymocyte differentiation in the thymus. The high-avidity interaction between TCR and self-peptide-MHC complexes induces development of regulatory T cells (Tregs), lineage commitment for which is controlled by expression of transcription factor Forkhead box P3 (FoxP3). The non-catalytic region of the tyrosine kinase (Nck) comprises two members, Nck1 and Nck2, with Nck1 playing a dominant role in TCR-mediated T cell activation and function. Nck's role, while established in thymocyte development, remains unelucidated in development of Tregs. In this study, we aimed to determine the function of Nck1 in the in vitro development and differentiation of human thymocytes. Human thymocytes were transfected with shRNA plasmid to silence Nck1 expression. The number of FoxP3+ Tregs decreased noticeably in Nck1 knockdown thymocytes after co-cultivation with myeloid dendritic cells (mDCs) and thymic epithelial cells for 14 days. Furthermore, decreased phosphorylation of AKT and FoxO1 was observed in Nck1-silenced thymocytes, in association with reduced FoxO1 nuclear localization. Taken together, these findings identify the pivotal role of Nck1 in Treg development.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}