Immunology最新文献

{"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><strong>Retraction: </strong>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,\" Immunology 110, 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The above article, published online on 22 August 2003 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Greg Delgoffe; and John Wiley & Sons Ltd.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.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"278"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ITGB4/BNIP3 Activates Autophagy and Reduces MHC-I Expression to Mediate Tumour Immune Escape in Pancreatic Cancer Cell Lines.","authors":"Xianfei Zhou, Fan Yang, Luoshun Huang, Yisheng Ling, Renwei Xing, Jie Lu, Hanqiu Nie","doi":"10.1111/imm.13890","DOIUrl":"10.1111/imm.13890","url":null,"abstract":"<p><p>This study attempted to identify the relevant pathways involved in autophagy activation of pancreatic cancer and explore the mechanisms underlying immune evasion. Western blot (WB) was used to detect the expression of ITGB4, BNIP3, autophagy-related proteins and MHC-I. Co-immunoprecipitation (Co-IP) was used to verify the binding mode of ITGB4 and BNIP3. Flow cytometry was used to detect the expression of MHC-I on the cell membrane. Transmission electron microscope (TEM) was used to observe cell autophagy. Confocal microscopy was used to observe the co-localisation relationship between MHC-I and autophagosomes in cells. ELISA was used to detect the level of lactate dehydrogenase and granzyme B in a tumour cell-CD8⁺ T-cell co-culture system. Mouse syngeneic transplant tumour model and orthotopic tumour model were constructed and treated with PD-1 monoclonal antibody to observe tumour growth. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of ITGB4 and BNIP3 in tumour tissues. WB was used to determine the expression of autophagy-related proteins. Flow cytometry was used to detect the expression of MHC-I on cell membranes and the proportion of CD3⁺ and CD8⁺ cells. The results of Co-IP experiments showed that ITGB4 could bind to BNIP3. It was observed under confocal microscopy that activating ITGB4/BNIP3 could promote the phagocytosis of MHC-I by autophagosomes. Finally, the subcutaneous tumour transplantation and orthotopic tumour experiments in mice demonstrated the downregulation of ITGB4 significantly improved the therapeutic effect of PD-1 antibodies on pancreatic cancer. In pancreatic cancer cells, autophagy is positively correlated with the ITGB4-BNIP3 complex protein expression level. Autophagy diminishes the protein expression of MHC-I, thereby promoting immune escape in pancreatic cancer cells.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"264-277"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876915","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}

{"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><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":" ","pages":"189-202"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"<p><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 (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.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"226-238"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","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}

{"title":"The Role of Wnt5a in Inflammatory Diseases.","authors":"Xin-Hua Yu, Xin-Ning Guo, Kui Li, Jia-Wei Li, Kaijin Wang, Dan Wang, Bi-Cui Liu","doi":"10.1111/imm.13882","DOIUrl":"10.1111/imm.13882","url":null,"abstract":"<p><p>Wnt5a plays an important role in cell development and maturation and is closely associated with various diseases, such as malignant tumours, metabolic disorders, fibrosis, growth and development. Recent studies have shown that Wnt5a expression and signal transduction are strongly involved in the inflammatory response. This study comprehensively reviewed the latest research progress on the association between Wnt5a and several inflammatory diseases, such as sepsis, asthma, chronic obstructive pulmonary disease, tuberculosis, rheumatoid arthritis, atherosclerosis and psoriasis vulgare. We elucidated the mechanism by which the Wnt5a protein is involved in the pathogenesis of these diseases, providing a basis for the prevention and treatment of inflammatory diseases.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"203-212"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817925","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}

{"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":"<p><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 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.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"213-225"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","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}

{"title":"Blocking Deoxycytidine Kinase in Activated Lymphocytes Depletes Deoxycytidine Triphosphate Pools and Alters Cell Cycle Kinetics to Yield Less Disease in a Mouse Multiple Sclerosis Model.","authors":"Jessica R Salas, K M Ryan, Alyssa O Trias, Bao Ying Chen, Miriam Guemes, Zoran Galic, Kenneth A Schultz, Peter M Clark","doi":"10.1111/imm.13885","DOIUrl":"10.1111/imm.13885","url":null,"abstract":"<p><p>Autoreactive, aberrantly activated lymphocytes that target myelin antigens in the central nervous system (CNS) are primary drivers of the autoimmune disease multiple sclerosis (MS). Proliferating cells including activated lymphocytes require deoxyribonucleoside triphosphates (dNTPs) for DNA replication. dNTPs can be synthesised via the de novo pathway from precursors such as glucose and amino acids or the deoxyribonucleoside salvage pathway from extracellular deoxyribonucleosides. Deoxycytidine kinase (dCK) is the rate-limiting enzyme in the salvage pathway. In prior work, we showed that targeting dCK with the small molecule inhibitor TRE-515 limits clinical symptoms in two myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) mouse models of MS and decreases the levels of activated CD4 T and B lymphocytes in vivo. However, whether targeting dCK limits disease in additional EAE models and how targeting dCK directly impacts activated and proliferating CD4 T and B cells has yet to be determined. Here, we show that dCK is activated in the lymph nodes and spleen in an EAE model induced by amino acids 139-151 of the proteolipid protein (PLP_139-151) that is driven by CD4 T and B cells and is characterised by acute disease followed by disease remission. Treating this model with TRE-515 limits clinical symptoms and decreases the levels of activated CD4 T and B cells. In culture, CD4 T and B cells induce deoxyribonucleoside salvage following activation, and TRE-515 directly blocks CD4 T and B cell activation-induced proliferation and activation marker expression. TRE-515 decreases deoxycytidine triphosphate (dCTP) and deoxythymidine triphosphate (dTTP) pools and increases the length of time cells spend in S phase of the cell cycle without inducing a replication stress response in B cells. Our results suggest that dCK activity is required to supply needed dNTPs and to enable rapid cell division following lymphocyte activation against autoantigens in EAE mouse models.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"247-263"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876941","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}

{"title":"The Role of Innate Immunity in Healthy Aging Through Antimicrobial Peptides.","authors":"Yejin Cho, Jeong-Hoon Hahm","doi":"10.1111/imm.13899","DOIUrl":"https://doi.org/10.1111/imm.13899","url":null,"abstract":"<p><p>In a super-aging society, the increase in the elderly population is closely tied to a rise in infectious diseases due to factors such as weakened immune systems and decreased vaccine efficacy in older adults. Various opportunistic pathogens commonly encountered in everyday life can cause infections and diseases when an individual's immune defence is weakened due to aging. These factors underscore the importance of preventive measures against pathogenic infections and the aging of immune systems in the elderly. The immune response acts as the defence mechanism against foreign substances, including pathogens and abnormal cells. Specifically, the innate immune response is the body's first line of defence, offering a rapid and nonspecific response to pathogens. Advances in the study of innate immunity's regulatory functions in both immune and non-immune cells have broadened our understanding of innate immune responses' impact on health. This includes a focus on immune effectors like antimicrobial peptides (AMPs) and their potential implications for health and longevity. This review summarises the common principles and evolutionary adaptations of innate immunity via AMPs, in mammals and invertebrates. Especially, this review discusses the conserved mechanisms regulating AMP production and the role of AMPs in modulating aging and diseases from invertebrate to human. Therefore, it highlights the potential role of innate immunity in addressing aging through AMPs.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004688","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}

{"title":"TYK2:p.Pro1104Ala Variant Protects Against Autoimmunity by Modulating Immune Cell Levels.","authors":"Maristella Steri, Valeria Orrù, Carlo Sidore, Antonella Mulas, Maristella Pitzalis, Fabio Busonero, Andrea Maschio, Valentina Serra, Mariano Dei, Sandra Lai, Francesca Virdis, Monia Lobina, Annalisa Loizedda, Michele Marongiu, Marco Masala, Matteo Floris, Nicolò Curreli, Lenuta Balaci, Francesco Loi, Maria Grazia Pilia, Alessandro Delitala, Edoardo Fiorillo, David Schlessinger, Magdalena Zoledziewska","doi":"10.1111/imm.13902","DOIUrl":"https://doi.org/10.1111/imm.13902","url":null,"abstract":"<p><p>The TYK2:p.Pro1104Ala (rs34536443) hypomorph variant has been associated with protection against numerous autoimmune disorders. Thus, its mechanism of action becomes of great interest. Here, consistent with the participation of activated immune cells in autoimmunity, we show that the variant regulates the levels of immune cells at a human, general population level and is associated particularly with higher levels of T and B lymphocytes, especially the naïve (non-activated) compartment. Also, consistent with a protective function in autoimmunity, the level of regulatory CD4+ T cells was increased. Thus, this variant decreases immune activation thereby protecting from autoimmunity. Our work links the cellular mechanism regulated by the TYK2:p.Pro1104Ala variant to autoimmunity protection and supports TYK2 as a therapeutic target in autoimmunity.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004694","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}

{"title":"IL-6 Signalling to Responding T Cells Is Key to Calcitonin Gene-Related Peptide-Exposed Endothelial Cell Enhancement of Th17 Immunity During Langerhans Cell Antigen Presentation.","authors":"Wanhong Ding, Cameron Moattari, Lori L Stohl, John A Wagner, Xi K Zhou, Richard D Granstein","doi":"10.1111/imm.13892","DOIUrl":"https://doi.org/10.1111/imm.13892","url":null,"abstract":"<p><p>Calcitonin gene-related peptide (CGRP) biases Langerhans cell (LC) Ag presentation to CD4⁺ T cells towards Th17-type immunity through actions on endothelial cells (ECs). We now report further evidence that IL-6 signalling at responding T cells mediates this effect. This CGRP effect was absent with ECs from IL-6 KO mice. Exposure of LCs, but not T cells, to IL-6 enhanced IL-6 and IL-17A production and reduced IFN-γ in the T-cell response. Pretreatment of LCs with IL-6 receptor α-chain (IL-6Rα) antibodies prior to IL-6 exposure significantly inhibited these responses. However, T-cell pretreatment with an IL-6/IL-6Rα chimera mimicked the effect of IL-6 pretreatment of LCs on T-cell responses. When this experiment was performed in the presence of the ADAM17 and ADAM10 inhibitor TAPI-1 during LC pretreatment of LCs and during the Ag presentation culture, release of soluble IL-6Rα chains into the medium was very significantly reduced, but this did not affect levels of T-cell cytokine release. Interestingly, LC exposure to IL-6 significantly increased LC IL-6 expression. Furthermore, pretreatment of T cells with antibodies against the IL-6 receptor β-chain significantly inhibited the IL-6 effect. CGRP may stimulate ECs in lymphatics and/or lymph nodes to produce IL-6 which likely results in migrating LCs nonclassically presenting IL-6. Furthermore, we found that IL-6 induces IL-6 production by LCs, suggesting an autocrine amplification pathway for this effect.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004683","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}