RETRACTION: S. Cuzzocrea, A. Rossi, I. Serraino, R. Di Paola, L. Dugo, T. Genovese, D. Britti, G. Sciarra, A. De Sarro, A. P. Caputi, and L. Sautebin, “ 5-lipoxygenase Knockout Mice Exhibit a Resistance to Acute Pancreatitis Induced by Cerulein,” Immunology110, no. 1 (2003): 120–130, https://doi.org/10.1046/j.1365-2567.2003.01715.x.
The above article, published online on 22 August 2003 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Greg Delgoffe; and John Wiley & Sons Ltd. The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Specifically, two panels of Figure 9 were found to have been previously published in articles with at least one common author and presented in a different scientific context. The article is retracted as the editors have lost trust in the accuracy and integrity of the overall body of data presented in the article and consider its conclusions invalid. No confirmation of the decision of retraction could be obtained by the authors.
撤回：S. Cuzzocrea, a . Rossi， I. Serraino， R. Di Paola， L. Dugo， T. Genovese， D. Britti， G. Sciarra, a . De Sarro, a . P. Caputi和L. Sautebin，“5-脂氧合酶敲除小鼠对Cerulein诱导的急性胰腺炎的抗性”，《免疫学》，第110期。1 (2003): 120-130, https://doi.org/10.1046/j.1365-2567.2003.01715.x。上述文章于2003年8月22日在线发表在Wiley在线图书馆（wileyonlinelibrary.com）上，经该杂志总编辑Greg Delgoffe同意撤回；及约翰威利父子有限公司。由于第三方对文章中提供的数据提出了担忧，已同意撤回。具体来说，我们发现图9中的两个面板之前发表在至少有一个共同作者的文章中，并且在不同的科学背景下呈现。由于编辑对文章中呈现的整体数据的准确性和完整性失去了信任，并认为其结论无效，因此文章被撤回。作者未得到撤稿决定的确认。
{"title":"RETRACTION: 5-lipoxygenase Knockout Mice Exhibit a Resistance to Acute Pancreatitis Induced by Cerulein","authors":"","doi":"10.1111/imm.13876","DOIUrl":"10.1111/imm.13876","url":null,"abstract":"<p>\u0000 \u0000 <b>RETRACTION</b>: <span>S. Cuzzocrea</span>, <span>A. Rossi</span>, <span>I. Serraino</span>, <span>R. Di Paola</span>, <span>L. Dugo</span>, <span>T. Genovese</span>, <span>D. Britti</span>, <span>G. Sciarra</span>, <span>A. De Sarro</span>, <span>A. P. Caputi</span>, and <span>L. Sautebin</span>, “ <span>5-lipoxygenase Knockout Mice Exhibit a Resistance to Acute Pancreatitis Induced by Cerulein</span>,” <i>Immunology</i> <span>110</span>, no. <span>1</span> (<span>2003</span>): <span>120</span>–<span>130</span>, https://doi.org/10.1046/j.1365-2567.2003.01715.x.\u0000 </p><p>The above article, published online on 22 August 2003 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Greg Delgoffe; and John Wiley & Sons Ltd. The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Specifically, two panels of Figure 9 were found to have been previously published in articles with at least one common author and presented in a different scientific context. The article is retracted as the editors have lost trust in the accuracy and integrity of the overall body of data presented in the article and consider its conclusions invalid. No confirmation of the decision of retraction could be obtained by the authors.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 2","pages":"278"},"PeriodicalIF":4.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785292","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}
RETRACTION: S. Cuzzocrea, A. P. Caputi, and B. Zingarelli, “ Peroxynitrite-mediated DNA Strand Breakage Activates Poly (ADP-ribose) Synthetase and Causes Cellular Energy Depletion in Carrageenan-induced Pleurisy,” Immunology93, no. 1 (1998): 96–101, https://doi.org/10.1046/j.1365-2567.1998.00409.x.
The above article, published online on 25 December 2001 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Greg Delgoffe; and John Wiley & Sons Ltd. The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Specifically, the Western Blot experiment in Figure 2 was found to have been presented in multiple publications with at least one common author and in a different scientific context. The article is retracted as the editors have lost trust in the accuracy and integrity of the overall body of data presented in the article and consider its conclusions invalid. No confirmation of the decision of retraction could be obtained by the authors.
引用本文：S. Cuzzocrea， A. P. Caputi和B. Zingarelli，“过氧亚硝酸盐介导的DNA链断裂激活聚腺苷核糖合成酶并引起卡拉胶性胸膜炎的细胞能量消耗”，《免疫学》93，no。1 (1998): 96-101, https://doi.org/10.1046/j.1365-2567.1998.00409.x。上述文章于2001年12月25日在Wiley在线图书馆（wileyonlinelibrary.com）上发表，经该杂志主编Greg Delgoffe同意撤回；及约翰威利父子有限公司。由于第三方对文章中提供的数据提出了担忧，已同意撤回。具体来说，图2中的Western Blot实验被发现出现在多个出版物中，至少有一个共同的作者，并且在不同的科学背景下。由于编辑对文章中呈现的整体数据的准确性和完整性失去了信任，并认为其结论无效，因此文章被撤回。作者未得到撤稿决定的确认。
{"title":"RETRACTION: Peroxynitrite-mediated DNA Strand Breakage Activates Poly (ADP-ribose) Synthetase and Causes Cellular Energy Depletion in Carrageenan-induced Pleurisy","authors":"","doi":"10.1111/imm.13877","DOIUrl":"10.1111/imm.13877","url":null,"abstract":"<p><b>RETRACTION</b>: <span>S. Cuzzocrea</span>, <span>A. P. Caputi</span>, and <span>B. Zingarelli</span>, “ <span>Peroxynitrite-mediated DNA Strand Breakage Activates Poly (ADP-ribose) Synthetase and Causes Cellular Energy Depletion in Carrageenan-induced Pleurisy</span>,” <i>Immunology</i> <span>93</span>, no. <span>1</span> (<span>1998</span>): <span>96</span>–<span>101</span>, https://doi.org/10.1046/j.1365-2567.1998.00409.x.</p><p>The above article, published online on 25 December 2001 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Greg Delgoffe; and John Wiley & Sons Ltd. The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Specifically, the Western Blot experiment in Figure 2 was found to have been presented in multiple publications with at least one common author and in a different scientific context. The article is retracted as the editors have lost trust in the accuracy and integrity of the overall body of data presented in the article and consider its conclusions invalid. No confirmation of the decision of retraction could be obtained by the authors.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 3","pages":"374"},"PeriodicalIF":4.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13877","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785271","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}
Bharati Matta, Jenna Battaglia, Margaret Lapan, Vinay Sharma, Betsy J. Barnes
Elevated levels of serum autoantibodies are a hallmark of systemic lupus erythematosus (SLE) and are produced by plasma cells in response to a variety of antigenic triggers. In SLE, the triggers are complex and may include both T cell-dependent/-independent and TLR-dependent/-independent mechanisms of immune activation, which ultimately contributes to the significant immune dysregulation seen in patients at the level of cytokine production and cellular activation (B cells, T cells, dendritic cells, neutrophils and macrophages). Interferon regulatory factor 5 (IRF5) has been identified as an autoimmune susceptibility gene and polymorphisms in IRF5 associate with altered expression and hyper-activation in distinct SLE immune cell subsets. To gain further insight into the mechanisms that drive IRF5-mediated SLE immune activation, we characterised wild-type (WT) and Irf5−/− Balb/c mice in response to immunisation. WT and Irf5−/− Balb/c mice were immunised to activate various signalling pathways in vivo followed by systemic immunophenotyping and detection of antibody production by multi-colour flow cytometry and ELISPOT. We identified two pathways, TLR9-dependent and T cell-dependent that resulted in IRF5 cell type-specific function. Immunisation with either CpG-B + Alum or NP-KLH + Alum but not with R848 + Alum, NP-LPS + Alum or NP-Ficoll+Alum resulted in decreased plasma cell generation and reduced antibody production in Irf5−/− mice. Notably, the mechanism(s) leading to this downstream phenotype was distinct. In CpG-B + Alum immunised mice, we found reduced activation of plasmacytoid dendritic cells, resulting in reduced IFNα and IL6 production in Irf5−/− mice. Conversely, mice immunised with NP-KLH + Alum had reduced numbers of T follicular helper cells and germinal centre B cells with reduced expression of Bcl6 in Irf5−/− mice. Moreover, T follicular helper cells from Irf5−/− mice were functionally defective. Even though the downstream phenotype of reduced antibody production in Irf5−/− mice was conserved between T cell-dependent and TLR9-dependent immunisation, the mechanisms leading to this phenotype were antigen- and cell type-specific.
{"title":"IRF5 Controls Plasma Cell Generation and Antibody Production via Distinct Mechanisms Depending on the Antigenic Trigger","authors":"Bharati Matta, Jenna Battaglia, Margaret Lapan, Vinay Sharma, Betsy J. Barnes","doi":"10.1111/imm.13879","DOIUrl":"10.1111/imm.13879","url":null,"abstract":"<div>\u0000 \u0000 <p>Elevated levels of serum autoantibodies are a hallmark of systemic lupus erythematosus (SLE) and are produced by plasma cells in response to a variety of antigenic triggers. In SLE, the triggers are complex and may include both T cell-dependent/-independent and TLR-dependent/-independent mechanisms of immune activation, which ultimately contributes to the significant immune dysregulation seen in patients at the level of cytokine production and cellular activation (B cells, T cells, dendritic cells, neutrophils and macrophages). Interferon regulatory factor 5 (<i>IRF5</i>) has been identified as an autoimmune susceptibility gene and polymorphisms in <i>IRF5</i> associate with altered expression and hyper-activation in distinct SLE immune cell subsets. To gain further insight into the mechanisms that drive IRF5-mediated SLE immune activation, we characterised wild-type (WT) and <i>Irf5</i>\u0000 <sup>−/−</sup> Balb/c mice in response to immunisation. WT and <i>Irf5</i>\u0000 <sup>−/−</sup> Balb/c mice were immunised to activate various signalling pathways in vivo followed by systemic immunophenotyping and detection of antibody production by multi-colour flow cytometry and ELISPOT. We identified two pathways, TLR9-dependent and T cell-dependent that resulted in IRF5 cell type-specific function. Immunisation with either CpG-B + Alum or NP-KLH + Alum but not with R848 + Alum, NP-LPS + Alum or NP-Ficoll+Alum resulted in decreased plasma cell generation and reduced antibody production in <i>Irf5</i>\u0000 <sup>−/−</sup> mice. Notably, the mechanism(s) leading to this downstream phenotype was distinct. In CpG-B + Alum immunised mice, we found reduced activation of plasmacytoid dendritic cells, resulting in reduced IFNα and IL6 production in <i>Irf5</i>\u0000 <sup>−/−</sup> mice. Conversely, mice immunised with NP-KLH + Alum had reduced numbers of T follicular helper cells and germinal centre B cells with reduced expression of Bcl6 in <i>Irf5</i>\u0000 <sup>−/−</sup> mice. Moreover, T follicular helper cells from <i>Irf5</i>\u0000 <sup>−/−</sup> mice were functionally defective. Even though the downstream phenotype of reduced antibody production in <i>Irf5</i>\u0000 <sup>−/−</sup> mice was conserved between T cell-dependent and TLR9-dependent immunisation, the mechanisms leading to this phenotype were antigen- and cell type-specific.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 2","pages":"226-238"},"PeriodicalIF":4.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cover illustration: The cover image is based on the article Advancement in the development of mRNA-based vaccines for respiratory viruses by Tays Troncoso-Bravo et al., https://doi.org/10.1111/imm.13844.
{"title":"Featured Cover","authors":"","doi":"10.1111/imm.13872","DOIUrl":"https://doi.org/10.1111/imm.13872","url":null,"abstract":"<p>Cover illustration: The cover image is based on the article <i>Advancement in the development of mRNA-based vaccines for respiratory viruses</i> by Tays Troncoso-Bravo et al., https://doi.org/10.1111/imm.13844.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 3","pages":"i"},"PeriodicalIF":4.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13872","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692089","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}
Mengfei Xue, Ruijie Yang, Guihong Li, Zhizhan Ni, Yuqing Chao, Kairui Shen, Hua Ren, Bing Du, Juliang Qin, Zhenliang Sun
Psoriasis is a chronic inflammatory skin disease characterised by inflammatory cell infiltration, keratinocyte hyperproliferation and increased neovascularization. Despite extensive research, the precise mechanisms underlying psoriasis pathology and treatment strategies remain unclear because of a complex aetiology and disease progression. Hence, in this study, we aimed to identify potential therapeutic targets for psoriasis and explore their effects on disease progression. We observed that G protein-coupled receptor LGR4 attenuates psoriasis progression. Bioinformatics analysis of publicly available clinical data revealed lower LGR4 expression in the skin lesions of patients with psoriasis than in their non-lesioned skin. Both in vitro (HaCaT cell) and in vivo (mouse) models confirmed this phenomenon. The Lgr4-knockout mouse model further confirmed that LGR4 plays a positive role in psoriasis progression. Specifically, Lgr4 knockout promoted the secretion of inflammatory factors, accumulation of local immunocyte infiltration in skin lesions, and keratinocyte proliferation. In conclusion, we demonstrated that LGR4 is critical to limiting psoriasis progression, suggesting that it is a viable target for the clinical management of this skin condition.
{"title":"LGR4 Deficiency Aggravates Skin Inflammation and Epidermal Hyperplasia in Imiquimod-Induced Psoriasis","authors":"Mengfei Xue, Ruijie Yang, Guihong Li, Zhizhan Ni, Yuqing Chao, Kairui Shen, Hua Ren, Bing Du, Juliang Qin, Zhenliang Sun","doi":"10.1111/imm.13873","DOIUrl":"10.1111/imm.13873","url":null,"abstract":"<div>\u0000 \u0000 <p>Psoriasis is a chronic inflammatory skin disease characterised by inflammatory cell infiltration, keratinocyte hyperproliferation and increased neovascularization. Despite extensive research, the precise mechanisms underlying psoriasis pathology and treatment strategies remain unclear because of a complex aetiology and disease progression. Hence, in this study, we aimed to identify potential therapeutic targets for psoriasis and explore their effects on disease progression. We observed that G protein-coupled receptor LGR4 attenuates psoriasis progression. Bioinformatics analysis of publicly available clinical data revealed lower LGR4 expression in the skin lesions of patients with psoriasis than in their non-lesioned skin. Both in vitro (HaCaT cell) and in vivo (mouse) models confirmed this phenomenon. The <i>Lgr4</i>-knockout mouse model further confirmed that LGR4 plays a positive role in psoriasis progression. Specifically, <i>Lgr4</i> knockout promoted the secretion of inflammatory factors, accumulation of local immunocyte infiltration in skin lesions, and keratinocyte proliferation. In conclusion, we demonstrated that LGR4 is critical to limiting psoriasis progression, suggesting that it is a viable target for the clinical management of this skin condition.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 2","pages":"213-225"},"PeriodicalIF":4.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sofía Dinamarca, Cristina Croce, Anna Salvioni, Facundo Garrido, Sandra Estrada Fidalgo, Gonzalo Bigliani, Luis S. Mayorga, Nicolas Blanchard, Ignacio Cebrian
Antigen cross-presentation is the process whereby small peptides derived from exogenous antigens are attached to MHC-I molecules triggering CD8+ T lymphocyte activation. The endocytic route of dendritic cells (DCs) is highly specialised for cross-presentation to initiate cytotoxic immune responses against numerous intracellular pathogens and tumours. In this study, we identify the endosomal protein sorting nexin (SNX) 17 as a key regulator of antigen internalisation and cross-presentation by DCs. SNX17 expression in DCs guarantees optimal cross-presentation of soluble, particulate, and Toxoplasma gondii-associated antigens. The silencing of SNX17 expression in DCs significantly affected the internalisation of exogenous antigens by fluid-phase endocytosis, phagocytosis, and more strikingly, T. gondii invasion. We show that SNX17 controls proper integrin recycling, actin cytoskeleton organisation, and phagosomal maturation. Altogether, our findings provide compelling evidence that SNX17 plays a central role in the modulation of the DC endocytic network, which is essential for competent antigen cross-presentation.
抗原交叉呈递是指来自外源性抗原的小肽附着在 MHC-I 分子上引发 CD8+ T 淋巴细胞活化的过程。树突状细胞（DCs）的内吞途径高度专业化，用于交叉呈递，启动针对多种细胞内病原体和肿瘤的细胞毒性免疫反应。在这项研究中，我们发现内泌体蛋白分选蛋白（SNX）17 是 DCs 抗原内化和交叉呈递的关键调节因子。SNX17在DC中的表达保证了可溶性、颗粒状和弓形虫相关抗原的最佳交叉呈递。抑制 SNX17 在直流细胞中的表达会显著影响外源抗原通过液相内吞、吞噬作用的内化，更显著的是会影响弓形虫的入侵。我们的研究表明，SNX17 控制着整合素的正常循环、肌动蛋白细胞骨架的组织以及吞噬体的成熟。总之，我们的研究结果提供了令人信服的证据，证明 SNX17 在调节 DC 内细胞网络中发挥着核心作用，而 DC 内细胞网络对有效的抗原交叉呈递至关重要。
{"title":"SNX17 Regulates Antigen Internalisation and Phagosomal Maturation by Dendritic Cells","authors":"Sofía Dinamarca, Cristina Croce, Anna Salvioni, Facundo Garrido, Sandra Estrada Fidalgo, Gonzalo Bigliani, Luis S. Mayorga, Nicolas Blanchard, Ignacio Cebrian","doi":"10.1111/imm.13878","DOIUrl":"10.1111/imm.13878","url":null,"abstract":"<div>\u0000 \u0000 <p>Antigen cross-presentation is the process whereby small peptides derived from exogenous antigens are attached to MHC-I molecules triggering CD8+ T lymphocyte activation. The endocytic route of dendritic cells (DCs) is highly specialised for cross-presentation to initiate cytotoxic immune responses against numerous intracellular pathogens and tumours. In this study, we identify the endosomal protein sorting nexin (SNX) 17 as a key regulator of antigen internalisation and cross-presentation by DCs. SNX17 expression in DCs guarantees optimal cross-presentation of soluble, particulate, and <i>Toxoplasma gondii</i>-associated antigens. The silencing of SNX17 expression in DCs significantly affected the internalisation of exogenous antigens by fluid-phase endocytosis, phagocytosis, and more strikingly, <i>T</i>. <i>gondii</i> invasion. We show that SNX17 controls proper integrin recycling, actin cytoskeleton organisation, and phagosomal maturation. Altogether, our findings provide compelling evidence that SNX17 plays a central role in the modulation of the DC endocytic network, which is essential for competent antigen cross-presentation.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 1","pages":"167-185"},"PeriodicalIF":4.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Itaconic acid and its metabolites have demonstrated significant therapeutic potential in various immune diseases. Originating from the tricarboxylic acid cycle in immune cells, itaconic acid can modulate immune responses, diminish inflammation, and combat oxidative stress. Recent research has uncovered multiple mechanisms through which itaconic acid exerts its effects, including the inhibition of inflammatory cytokine production, activation of anti-inflammatory pathways, and modulation of immune cell function by regulating cellular metabolism. Cellular actions are influenced by the modulation of metabolic pathways, such as inhibiting succinate dehydrogenase (SDH) activity or glycolysis, activation of nuclear-factor-E2-related factor 2 (Nrf2), boosting cellular defences against oxidative stress, and suppression of immune cell inflammation through the NF-κB pathway. This comprehensive review discusses the initiation, progression, and mechanisms of action of itaconic acid and its metabolites, highlighting their modulatory effects on various immune cell types. Additionally, it examines their involvement in immune disease like rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, and autoimmune hepatitis, offering greater understanding for creating new therapies for these ailments.
{"title":"Metabolic Regulation of Inflammation: Exploring the Potential Benefits of Itaconate in Autoimmune Disorders","authors":"Yin Luo, Li-Yan Jiang, Zhe-Zhen Liao, Yuan-Yuan Wang, Ya-Di Wang, Xin-Hua Xiao","doi":"10.1111/imm.13875","DOIUrl":"10.1111/imm.13875","url":null,"abstract":"<p>Itaconic acid and its metabolites have demonstrated significant therapeutic potential in various immune diseases. Originating from the tricarboxylic acid cycle in immune cells, itaconic acid can modulate immune responses, diminish inflammation, and combat oxidative stress. Recent research has uncovered multiple mechanisms through which itaconic acid exerts its effects, including the inhibition of inflammatory cytokine production, activation of anti-inflammatory pathways, and modulation of immune cell function by regulating cellular metabolism. Cellular actions are influenced by the modulation of metabolic pathways, such as inhibiting succinate dehydrogenase (SDH) activity or glycolysis, activation of nuclear-factor-E2-related factor 2 (Nrf2), boosting cellular defences against oxidative stress, and suppression of immune cell inflammation through the NF-κB pathway. This comprehensive review discusses the initiation, progression, and mechanisms of action of itaconic acid and its metabolites, highlighting their modulatory effects on various immune cell types. Additionally, it examines their involvement in immune disease like rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, and autoimmune hepatitis, offering greater understanding for creating new therapies for these ailments.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 2","pages":"189-202"},"PeriodicalIF":4.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13875","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619370","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":"Coexistence of IL12Rβ1 and BTK Mutations in a Family","authors":"Hulya Kose, Orhan Gorukmez, Sara Sebnem Kilic","doi":"10.1111/imm.13874","DOIUrl":"10.1111/imm.13874","url":null,"abstract":"","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 1","pages":"186-188"},"PeriodicalIF":4.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Durre Aden, Niti Sureka, Samreen Zaheer, Jai Kumar Chaurasia, Sufian Zaheer
Cancer is a complex and heterogeneous disease characterised by uncontrolled cell growth and proliferation. One hallmark of cancer cells is their ability to undergo metabolic reprogramming, which allows them to sustain their rapid growth and survival. This metabolic reprogramming creates an immunosuppressive microenvironment that facilitates tumour progression and evasion of the immune system. In this article, we review the mechanisms underlying metabolic reprogramming in cancer cells and discuss how these metabolic alterations contribute to the establishment of an immunosuppressive microenvironment. We also explore potential therapeutic strategies targeting metabolic vulnerabilities in cancer cells to enhance immune-mediated anti-tumour responses.
{"title":"Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment","authors":"Durre Aden, Niti Sureka, Samreen Zaheer, Jai Kumar Chaurasia, Sufian Zaheer","doi":"10.1111/imm.13871","DOIUrl":"10.1111/imm.13871","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Cancer is a complex and heterogeneous disease characterised by uncontrolled cell growth and proliferation. One hallmark of cancer cells is their ability to undergo metabolic reprogramming, which allows them to sustain their rapid growth and survival. This metabolic reprogramming creates an immunosuppressive microenvironment that facilitates tumour progression and evasion of the immune system. In this article, we review the mechanisms underlying metabolic reprogramming in cancer cells and discuss how these metabolic alterations contribute to the establishment of an immunosuppressive microenvironment. We also explore potential therapeutic strategies targeting metabolic vulnerabilities in cancer cells to enhance immune-mediated anti-tumour responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT02044861, NCT03163667, NCT04265534, NCT02071927, NCT02903914, NCT03314935, NCT03361228, NCT03048500, NCT03311308, NCT03800602, NCT04414540, NCT02771626, NCT03994744, NCT03229278, NCT04899921</p>\u0000 </section>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 1","pages":"30-72"},"PeriodicalIF":4.9,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13871","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499556","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}
Rachel Coulombeau, Claudia Selck, Nicolas Giang, Abdulrahman Al-Mohammad, Natalie Ng, Allison K. Maher, Rafael Argüello, Antonio Scalfari, James Varley, Richard Nicholas, Margarita Dominguez-Villar
Inflammatory environments induce the generation of dysfunctional IFNγ+T-bet+FOXP3+ Th1-like Tregs, which show defective function and are found in autoimmune conditions including multiple sclerosis (MS). The pathways that control the generation of Th1-like Tregs are not well understood. Sphingosine-1-phosphate (S1P) signalling molecules are upregulated in Th1-like Tregs, and in vivo S1P inhibition with Fingolimod (FTY720) inhibits the expression of genes responsible for Treg plasticity in MS patients. However, the underlying mechanisms are unknown. Here we show that S1P signalling inhibition by FTY720 inhibits the generation of Th1-like Tregs and rescues their suppressive function. These effects are mediated by a decrease in mTORC1 signalling and reversal of the mitochondrial uncoupling that Tregs undergo during their reprogramming into Th1-like Tregs in vitro. Finally, these results are validated in in vivo-generated Th1-like Tregs, as Tregs from MS patients treated with FTY720 display decreased Th1-like Treg frequency, increased suppressive function and mitochondrial metabolism rebalance. These results highlight the involvement of mitochondrial uncoupling in Treg reprogramming and identify S1P signalling inhibition as a target to suppress the generation of dysfunctional Th1-like Tregs.
{"title":"Sphingosine-1-Phosphate Signalling Inhibition Suppresses Th1-Like Treg Generation by Reversing Mitochondrial Uncoupling","authors":"Rachel Coulombeau, Claudia Selck, Nicolas Giang, Abdulrahman Al-Mohammad, Natalie Ng, Allison K. Maher, Rafael Argüello, Antonio Scalfari, James Varley, Richard Nicholas, Margarita Dominguez-Villar","doi":"10.1111/imm.13870","DOIUrl":"10.1111/imm.13870","url":null,"abstract":"<p>Inflammatory environments induce the generation of dysfunctional IFNγ<sup>+</sup>T-bet<sup>+</sup>FOXP3<sup>+</sup> Th1-like Tregs, which show defective function and are found in autoimmune conditions including multiple sclerosis (MS). The pathways that control the generation of Th1-like Tregs are not well understood. Sphingosine-1-phosphate (S1P) signalling molecules are upregulated in Th1-like Tregs, and in vivo S1P inhibition with Fingolimod (FTY720) inhibits the expression of genes responsible for Treg plasticity in MS patients. However, the underlying mechanisms are unknown. Here we show that S1P signalling inhibition by FTY720 inhibits the generation of Th1-like Tregs and rescues their suppressive function. These effects are mediated by a decrease in mTORC1 signalling and reversal of the mitochondrial uncoupling that Tregs undergo during their reprogramming into Th1-like Tregs in vitro. Finally, these results are validated in in vivo-generated Th1-like Tregs, as Tregs from MS patients treated with FTY720 display decreased Th1-like Treg frequency, increased suppressive function and mitochondrial metabolism rebalance. These results highlight the involvement of mitochondrial uncoupling in Treg reprogramming and identify S1P signalling inhibition as a target to suppress the generation of dysfunctional Th1-like Tregs.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 1","pages":"153-166"},"PeriodicalIF":4.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499557","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}
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