Immunology letters最新文献

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The importance of type I interferon in orchestrating the cytotoxic T-cell response to cancer I 型干扰素在协调细胞毒性 T 细胞对癌症的反应中的重要性
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-10-28 DOI: 10.1016/j.imlet.2024.106938
Julia Busselaar , Merel Sijbranda , Jannie Borst
{"title":"The importance of type I interferon in orchestrating the cytotoxic T-cell response to cancer","authors":"Julia Busselaar ,&nbsp;Merel Sijbranda ,&nbsp;Jannie Borst","doi":"10.1016/j.imlet.2024.106938","DOIUrl":"10.1016/j.imlet.2024.106938","url":null,"abstract":"<div><div>Both type I interferon (IFN-I) and CD4<sup>+</sup> T-cell help are required to generate effective CD8<sup>+</sup> T-cell responses to cancer. We here outline based on existing literature how IFN-I signaling and CD4<sup>+</sup> T-cell help are connected. Both impact on the functional state of dendritic cells (DCs), particularly conventional (c)DC1. The cDC1s are critical for crosspresentation of cell-associated antigens and for delivery of CD4<sup>+</sup> T-cell help for cytotoxic T-lymphocyte (CTL) effector and memory differentiation. In infection, production of IFN-I is prompted by pathogen-associated molecular patterns (PAMPs), while in cancer it relies on danger-associated molecular patterns (DAMPs). IFN-I production by tumor cells and pDCs in the tumor micro-environment (TME) is often limited. IFN-I signals increase the ability of migratory cDC1s and cDC2s to transport tumor antigens to tumor-draining lymph nodes (tdLNs). IFN-I also enables cDC1s to form and sustain the platform for help delivery by stimulating the production of chemokines that attract CD4<sup>+</sup> and CD8<sup>+</sup> T cells. IFN-I promotes delivery of help in concert with CD40 signals by additive and synergistic impact on cross-presentation and provision of critical costimulatory and cytokine signals for CTL effector and memory differentiation. The scenario of CD4<sup>+</sup> T-cell help therefore depends on IFN-I signaling. This scenario can play out in tdLNs as well as in the TME, thereby contributing to the cancer immunity cycle. The collective observations may explain why both IFN-I and CD4<sup>+</sup> T-cell help signatures in the TME correlate with good prognosis and response to PD-1 targeting immunotherapy in human cancer. They also may explain why a variety of tumor types in which IFN-I signaling is attenuated, remain devoid of functional CTLs.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106938"},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560883","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}
引用次数: 0
Study of the mechanism of fibroblast-like synoviocytes-derived exosomes inducing macrophages M1 polarization and CD8+T cells immune regulation ferroptosis and autophagy in rheumatoid arthritis 成纤维细胞样滑膜细胞外泌体诱导类风湿性关节炎巨噬细胞M1极化和CD8+T细胞免疫调节铁蛋白沉积及自噬的机制研究
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-10-22 DOI: 10.1016/j.imlet.2024.106936
Fang Fang , Mengqing Hua , GenMing Yu
{"title":"Study of the mechanism of fibroblast-like synoviocytes-derived exosomes inducing macrophages M1 polarization and CD8+T cells immune regulation ferroptosis and autophagy in rheumatoid arthritis","authors":"Fang Fang ,&nbsp;Mengqing Hua ,&nbsp;GenMing Yu","doi":"10.1016/j.imlet.2024.106936","DOIUrl":"10.1016/j.imlet.2024.106936","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the joints. The pathogenesis of RA is complex, involving membrane lipid antioxidant systems, oxidative stress, and lipid peroxidation. In this study, it was found that cysteine dioxygenase 1 (CDO1) is significantly upregulated in RA fibroblast-like synoviocytes (RA-FLS) and that exosomes derived from these RA-FLS deliver CDO1 to promote M1 polarization of macrophages, thus facilitating RA progression. In the immune microenvironment, CD8<sup>+</sup><em>T</em> cells play a role in immune regulation by producing cytokines such as interferon gamma (IFNγ) in various diseases. The results of this study suggested that in RA-FLS, CD8<sup>+</sup><em>T</em> cells deliver IFNγ, which not only inhibits the viability of RA-FLS but also affects glutathione (GSH) through CDO1, regulating the GPX4 antioxidant signaling pathway to promote ferroptosis and autophagy in cells. It was also discovered that IFNγ enhances the expression of TRI69, ubiquitinates and degrades FSP1, thereby forming a cooperative regulation process of GPX4 and FSP1 in ferroptosis. These findings provide a new direction for the treatment of RA.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106936"},"PeriodicalIF":3.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499545","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}
引用次数: 0
Fingolimod, an antagonist of sphingosine 1-phosphate, ameliorates Sjögren's syndrome by reducing the number of STAT3–induced germinal center B cells and increasing the number of Breg cells 鞘氨醇1-磷酸拮抗剂芬戈莫德可通过减少STAT3诱导的生殖中心B细胞数量和增加Breg细胞数量来改善Sjögren综合征。
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-10-11 DOI: 10.1016/j.imlet.2024.106935
Yeon Su Lee , JooYeon Jhun , Jeong Won Choi , Sun-Hee Hwang , Jin Seok Woo , Kun Hee Lee , Seung Cheon Yang , A. Ram Lee , Mi-La Cho
{"title":"Fingolimod, an antagonist of sphingosine 1-phosphate, ameliorates Sjögren's syndrome by reducing the number of STAT3–induced germinal center B cells and increasing the number of Breg cells","authors":"Yeon Su Lee ,&nbsp;JooYeon Jhun ,&nbsp;Jeong Won Choi ,&nbsp;Sun-Hee Hwang ,&nbsp;Jin Seok Woo ,&nbsp;Kun Hee Lee ,&nbsp;Seung Cheon Yang ,&nbsp;A. Ram Lee ,&nbsp;Mi-La Cho","doi":"10.1016/j.imlet.2024.106935","DOIUrl":"10.1016/j.imlet.2024.106935","url":null,"abstract":"<div><h3>Background</h3><div>Sjögren's syndrome (SS) is an autoimmune disease caused by infiltrating lymphocytes. FTY720 affects the S1P signaling pathway, which plays a role in T and B cell migration from secondary lymphoid tissues to target organs. In this study, we investigate the regulatory mechanism of FTY720 in the context of SS.</div></div><div><h3>Method</h3><div>FTY720 was given orally every day to NOD mice. The salivary flow rate (SFR) and blood glucose level were assayed every 3 weeks. Histopathological features were investigated at the end of the study. In vitro, FTY720 was added to mouse splenocytes, and changes in the lymphocyte subsets were assessed.</div></div><div><h3>Results</h3><div>In vivo, FTY720 increased the SFR and reduced the blood glucose level. The salivary gland histological score and infiltration of the salivary glands by B and T cells were dramatically decreased. Furthermore, STAT expression in the salivary gland was decreased. In vitro, FTY720 inhibited Th17 cells, while increasing regulatory T (Treg) cells, respectively. Also, FTY720 decreased and increased the numbers of germinal center (GC) B cells and regulatory B cells (Breg cells), respectively. FTY720 decreased the IgG level in culture supernatants. Also, STAT3 activation was decreased by FTY720.</div></div><div><h3>Conclusion</h3><div>Our results show the therapeutic potential of FTY720 in the context of SS; FTY720 prevents lymphocyte migration from secondary lymphoid organs to target organs.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106935"},"PeriodicalIF":3.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464251","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}
引用次数: 0
Ursolic acid attenuates pseudo-allergic reactions via reducing MRGPRX2-mediated mast cell degranulation 熊果酸通过减少 MRGPRX2 介导的肥大细胞脱颗粒来减轻假性过敏反应
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-10-10 DOI: 10.1016/j.imlet.2024.106934
Ping-ping Yan , Ting-ting Huang , Si-yu Liu , Mawusse K.I. Attiogbe , Yan-ni Liu , Fan-qi Shen , Yan-ni Mi , Yong-xiao Cao
{"title":"Ursolic acid attenuates pseudo-allergic reactions via reducing MRGPRX2-mediated mast cell degranulation","authors":"Ping-ping Yan ,&nbsp;Ting-ting Huang ,&nbsp;Si-yu Liu ,&nbsp;Mawusse K.I. Attiogbe ,&nbsp;Yan-ni Liu ,&nbsp;Fan-qi Shen ,&nbsp;Yan-ni Mi ,&nbsp;Yong-xiao Cao","doi":"10.1016/j.imlet.2024.106934","DOIUrl":"10.1016/j.imlet.2024.106934","url":null,"abstract":"<div><div>Mas-related G protein–coupled receptor X2 (MRGPRX2) is a newly identified receptor on mast cells that contribute to IgE-independent pseudo-allergy. Ursolic acid (UA), a pentacyclic triterpenoid, has been reported for its anti-allergy effects. However, the protective mechanism against pseudo-allergic reactions remains unclear. This study aims to investigate the effects of UA on pseudo-allergic reactions both <em>in vivo</em> and <em>in vitro</em>, focusing on the therapeutical mechanism underlying its effect on mast cells. In present study, UA reduced degranulation and chemokines production induced by MRGPRX2 agonists, including compound 48/80 (C48/80) and substance P (SP), in LAD2 cells <em>in vitro</em>. UA also alleviated C48/80 and SP-induced systemic anaphylaxis and passive cutaneous anaphylaxis (PCA) <em>in vivo</em>. Furthermore, UA demonstrated strong binding affinity to the MRGPRX2 protein, leading to a decrease in calcium influx in both LAD2 cells and MRGPRX2-HEK293 cells stimulated with C48/80 and SP. Moreover, UA effectively suppressed phosphorylation levels within phospholipase C-γ (PLCγ) pathway and nuclear factor kappa-B (NF-κB) pathway of MRGPRX2 downstream proteins. Our findings indicated that UA exerts an attenuating effect in pseudo-allergic reactions by suppressing MRGPRX2-mediated mast cell activation, targeting PLCγ pathway and NF-κB pathway. These results suggest that UA may serve as a promising therapeutic agent for MRGPRX2-dependent pseudo-allergic reactions.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106934"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441805","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}
引用次数: 0
The role of neutrophils in ANCA-associated vasculitis 中性粒细胞在 ANCA 相关性血管炎中的作用
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-10-01 DOI: 10.1016/j.imlet.2024.106933
Maria Prendecki, Angila Gurung, Noelle Pisacano, Charles D. Pusey
{"title":"The role of neutrophils in ANCA-associated vasculitis","authors":"Maria Prendecki,&nbsp;Angila Gurung,&nbsp;Noelle Pisacano,&nbsp;Charles D. Pusey","doi":"10.1016/j.imlet.2024.106933","DOIUrl":"10.1016/j.imlet.2024.106933","url":null,"abstract":"<div><div>Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a group of rare systemic autoimmune diseases characterised by necrotising inflammation of small blood vessels and usually associated with circulating ANCA. The pathophysiology of AAV is complex, involving many aspects of the innate and adaptive immune system. Neutrophils are central to the pathogenesis of AAV as they are both the target of the autoantibody and effector cells mediating vascular injury. We describe mechanisms for ANCA induced activation of neutrophils, the pathogenic mechanisms by which this leads to endothelial cell injury, and how neutrophil crosstalk modulates other aspects of the immune system in AAV.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106933"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371741","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}
引用次数: 0
Fighting the enemy within: Systemic immune defense against mucosal Salmonella infection 与内部敌人作战:针对粘膜沙门氏菌感染的全身免疫防御。
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-09-27 DOI: 10.1016/j.imlet.2024.106930
Alana T. Nguyen, Stephen J. McSorley
{"title":"Fighting the enemy within: Systemic immune defense against mucosal Salmonella infection","authors":"Alana T. Nguyen,&nbsp;Stephen J. McSorley","doi":"10.1016/j.imlet.2024.106930","DOIUrl":"10.1016/j.imlet.2024.106930","url":null,"abstract":"<div><div><em>Salmonella</em> infection remains a persistent global health threat, as different serovars induce a range of clinical disease, depending upon bacterial virulence and host susceptibility. While some <em>Salmonella</em> serovars induce gastroenteritis in healthy individuals, others can cause more serious systemic enteric fever or invasive nontyphoidal Salmonellosis. The rise of antibiotic resistance, coupled with the absence of effective vaccines for most serovars, perpetuates the spread of <em>Salmonella</em> in endemic regions. A detailed mechanistic understanding of immunity to <em>Salmonella</em> infections has been aided by the availability of mouse models that have served as a valuable tool for understanding host-pathogen interactions under controlled laboratory conditions. These mouse studies have delineated the processes by which early inflammation is triggered after infection, how adaptive immunity is initiated in lymphoid tissues, and the contribution of lymphocyte memory responses to resistance. While recent progress has been made in vaccine development for some causes of enteric fever, deeper understanding of <em>Salmonella</em>-specific immune memory might allow the formation of new vaccines for all serovars. This review will provide a summary of our understanding of vaccination and protective immunity to <em>Salmonella</em> with a focus on recent developments in T cell memory formation.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106930"},"PeriodicalIF":3.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345945","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}
引用次数: 0
Reassuring humoral and cellular immune responses to SARS-CoV-2 vaccination in participants with systemic sclerosis 系统性硬化症患者对 SARS-CoV-2 疫苗接种的体液和细胞免疫反应令人放心。
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-09-19 DOI: 10.1016/j.imlet.2024.106929
Jenna M. Benoit , Jessica A. Breznik , Angela Huynh , Braeden Cowbrough , Barbara Baker , Lauren Heessels , Sumiya Lodhi , Elizabeth Yan , Hina Bhakta , Rumi Clare , Ishac Nazy , Jonathan L. Bramson , Maggie J. Larché , Dawn ME Bowdish
{"title":"Reassuring humoral and cellular immune responses to SARS-CoV-2 vaccination in participants with systemic sclerosis","authors":"Jenna M. Benoit ,&nbsp;Jessica A. Breznik ,&nbsp;Angela Huynh ,&nbsp;Braeden Cowbrough ,&nbsp;Barbara Baker ,&nbsp;Lauren Heessels ,&nbsp;Sumiya Lodhi ,&nbsp;Elizabeth Yan ,&nbsp;Hina Bhakta ,&nbsp;Rumi Clare ,&nbsp;Ishac Nazy ,&nbsp;Jonathan L. Bramson ,&nbsp;Maggie J. Larché ,&nbsp;Dawn ME Bowdish","doi":"10.1016/j.imlet.2024.106929","DOIUrl":"10.1016/j.imlet.2024.106929","url":null,"abstract":"<div><div>Individuals with systemic sclerosis (SSc) are particularly susceptible to SARS-CoV-2 infections, yet it remains to be determined if they generate humoral and cellular responses comparable to controls following SARS-CoV-2 vaccinations. Herein, we collected blood and serum after second, third, and fourth SARS-CoV-2 vaccinations in patients with SSc and controls. Following each dose, participants with SSc mounted comparable serum anti-RBD IgG, anti-RBD IgA, and spike-specific CD4<sup>+</sup> and CD8<sup>+</sup> <em>T</em> cell responses to those found in controls. At 3 months post dose 2, the frequencies of Th1, Th2, Th17, and Treg spike-specific CD4<sup>+</sup> <em>T</em> cells in participants with SSc did not differ from controls. At 2–6 weeks post dose 3, participants with SSc displayed reduced frequencies, but not numbers, of Th17-polarized spike-specific CD4<sup>+</sup> <em>T</em> cells. Thus, participants with SSc did not display significantly weaker humoral or cellular responses to SARS-CoV-2 vaccination than controls, enabling reassurance of vaccine immunogenicity in participants with SSc.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106929"},"PeriodicalIF":3.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286178","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}
引用次数: 0
NK cell receptors in anti-tumor and healthy tissue protection: Mechanisms and therapeutic advances 抗肿瘤和保护健康组织中的 NK 细胞受体:机制与治疗进展。
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-09-18 DOI: 10.1016/j.imlet.2024.106932
Marco Greppi , Fabiana De Franco , Valentina Obino , Federico Rebaudi , Rayan Goda , Davide Frumento , Giorgio Vita , Camilla Baronti , Ombretta Melaiu , Matteo Bozzo , Simona Candiani , Valerio G. Vellone , Federica Papaccio , Silvia Pesce , Emanuela Marcenaro
{"title":"NK cell receptors in anti-tumor and healthy tissue protection: Mechanisms and therapeutic advances","authors":"Marco Greppi ,&nbsp;Fabiana De Franco ,&nbsp;Valentina Obino ,&nbsp;Federico Rebaudi ,&nbsp;Rayan Goda ,&nbsp;Davide Frumento ,&nbsp;Giorgio Vita ,&nbsp;Camilla Baronti ,&nbsp;Ombretta Melaiu ,&nbsp;Matteo Bozzo ,&nbsp;Simona Candiani ,&nbsp;Valerio G. Vellone ,&nbsp;Federica Papaccio ,&nbsp;Silvia Pesce ,&nbsp;Emanuela Marcenaro","doi":"10.1016/j.imlet.2024.106932","DOIUrl":"10.1016/j.imlet.2024.106932","url":null,"abstract":"<div><div>Natural Killer (NK) cells are integral to the innate immune system, renowned for their ability to target and eliminate cancer cells without the need for antigen presentation, sparing normal tissues. These cells are crucial in cancer immunosurveillance due to their diverse array of activating and inhibitory receptors that modulate their cytotoxic activity. However, the tumor microenvironment can suppress NK cell function through various mechanisms. Over recent decades, research has focused on overcoming these tumor escape mechanisms. Initially, efforts concentrated on enhancing T cell activity, leading to impressive results with immunotherapeutic approaches aimed at boosting T cell responses. Nevertheless, a substantial number of patients do not benefit from these treatments and continue to seek effective alternatives. In this context, NK cells present a promising avenue for developing new treatments, given their potent cytotoxic capabilities, safety profile, and activity against T cell-resistant tumors, such as those lacking HLA-I expression. Recent advancements in immunotherapy include strategies to restore and amplify NK cell activity through immune checkpoint inhibitors, cytokines, adoptive NK cell therapy, and CAR-NK cell technology. This review provides a comprehensive overview of NK cell receptors, the tumor escape mechanisms that hinder NK cell function, and the evolving field of NK cell-based cancer immunotherapy, highlighting ongoing efforts to develop more effective and targeted cancer treatment strategies.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106932"},"PeriodicalIF":3.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824001068/pdfft?md5=d43348cfcc26cd5b9229bd583314ccfb&pid=1-s2.0-S0165247824001068-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286180","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}
引用次数: 0
Gene therapy strategies for RAG1 deficiency: Challenges and breakthroughs RAG1 缺乏症的基因治疗策略:挑战与突破。
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-09-18 DOI: 10.1016/j.imlet.2024.106931
Giorgio Gilioli , Arjan C. Lankester , Sander de Kivit , Frank J.T. Staal , Lisa M. Ott de Bruin
{"title":"Gene therapy strategies for RAG1 deficiency: Challenges and breakthroughs","authors":"Giorgio Gilioli ,&nbsp;Arjan C. Lankester ,&nbsp;Sander de Kivit ,&nbsp;Frank J.T. Staal ,&nbsp;Lisa M. Ott de Bruin","doi":"10.1016/j.imlet.2024.106931","DOIUrl":"10.1016/j.imlet.2024.106931","url":null,"abstract":"<div><div>Mutations in the recombination activating genes (RAG) cause various forms of immune deficiency. Hematopoietic stem cell transplantation (HSCT) is the only cure for patients with severe manifestations of RAG deficiency; however, outcomes are suboptimal with mismatched donors. Gene therapy aims to correct autologous hematopoietic stem and progenitor cells (HSPC) and is emerging as an alternative to allogeneic HSCT. Gene therapy based on viral gene addition exploits viral vectors to add a correct copy of a mutated gene into the genome of HSPCs. Only recently, after a prolonged phase of development, viral gene addition has been approved for clinical testing in RAG1-SCID patients. In the meantime, a new technology, CRISPR/Cas9, has made its debut to compete with viral gene addition. Gene editing based on CRISPR/Cas9 allows to perform targeted genomic integrations of a correct copy of a mutated gene, circumventing the risk of virus-mediated insertional mutagenesis. In this review, we present the biology of the <em>RAG</em> genes, the challenges faced during the development of viral gene addition for RAG1-SCID, and the current status of gene therapy for RAG1 deficiency. In particular, we highlight the latest advances and challenges in CRISPR/Cas9 gene editing and their potential for the future of gene therapy.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106931"},"PeriodicalIF":3.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286177","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}
引用次数: 0
The alpha2-adrenoceptor agonist clonidine protects against hypoxic-ischemic brain damage in neonatal mice through the Nrf2/NF-κB signaling pathway α2-肾上腺素受体激动剂氯尼丁通过Nrf2/NF-κB信号通路保护新生小鼠免受缺氧缺血性脑损伤。
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-09-17 DOI: 10.1016/j.imlet.2024.106928
Daojing Su , Huan Gao , Min He , Hu Hao , Heng Liao , Su Zheng
{"title":"The alpha2-adrenoceptor agonist clonidine protects against hypoxic-ischemic brain damage in neonatal mice through the Nrf2/NF-κB signaling pathway","authors":"Daojing Su ,&nbsp;Huan Gao ,&nbsp;Min He ,&nbsp;Hu Hao ,&nbsp;Heng Liao ,&nbsp;Su Zheng","doi":"10.1016/j.imlet.2024.106928","DOIUrl":"10.1016/j.imlet.2024.106928","url":null,"abstract":"<div><div>Neonatal hypoxic-ischemic brain damage (HIBD) is a severe condition closely associated with neuroinflammation and oxidative stress. Clonidine, a selective α2-adrenergic receptor agonist, is known for its anti-inflammatory and antioxidant properties. Despite these recognized therapeutic benefits, the exact mechanisms by which clonidine exerts its effects in the context of HIBD are not fully understood. This study was designed to thoroughly investigate the impact of clonidine on HIBD-induced neuronal injury and to clarify its underlying mechanism of action. We employed a neonatal mouse model of HIBD to meticulously assess the effects of clonidine on neuronal injury, apoptosis, inflammation, and oxidative stress markers. In addition, we conducted extensive <em>in vitro</em> studies to evaluate the neuroprotective effects of clonidine on primary hippocampal neuronal cells, utilizing advanced techniques such as the Cell Counting Kit-8 (CCK-8), flow cytometry, enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay, and western blotting. Furthermore, we explored the regulatory effects of clonidine on the nuclear factor erythroid 2-related factor (Nrf2)/nuclear factor-κB (NF-κB) signaling pathway through a combination of <em>in vivo</em> and <em>in vitro</em> experiments. The results showed that clonidine significantly reduced cerebral infarction, neuronal damage, and apoptosis in HIBD mice. It also alleviated neuroinflammation and oxidative stress, improved cell viability, and reduced neuronal injury following oxygen-glucose deprivation/reoxygenation (OGD/R). The neuroprotective effects of clonidine were linked to the activation of the Nrf2/heme oxygenase-1 (HO-1) pathway and the inhibition of the NF-κB pathway. Overall, clonidine exhibited neuroprotective properties in HIBD by reducing neuroinflammation and oxidative stress, likely through the modulation of the Nrf2/NF-κB signaling pathway.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106928"},"PeriodicalIF":3.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286179","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}
引用次数: 0
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