Immunology最新文献

{"title":"Unravelling CD24-Siglec-10 pathway: Cancer immunotherapy from basic science to clinical studies","authors":"Rudradeep Hazra,&nbsp;Soumyadeep Chattopadhyay,&nbsp;Arijit Mallick,&nbsp;Sakuntala Gayen,&nbsp;Souvik Roy","doi":"10.1111/imm.13847","DOIUrl":"10.1111/imm.13847","url":null,"abstract":"<p>Cancer immunotherapy has revolutionized the treatment landscape by harnessing the power of the immune system to combat malignancies. Two of the most promising players in this field are cluster of differentiation 24 (CD24) and sialic acid-binding Ig-like lectin 10 (Siglec-10), and both of them play pivotal roles in modulating immune responses. CD24, a cell surface glycoprotein, emerges as a convincing fundamental signal transducer for therapeutic intervention, given its significant implication in the processes related to tumour progression and immunogenic evasion. Additionally, the immunomodulatory functions of Siglec-10, a prominent member within the Siglec family of immune receptors, have recently become a crucial point of interest, particularly in the context of the tumour microenvironment. Hence, the intricate interplay of both CD24 and Siglec-10 assumes a critical role in fostering tumour growth, facilitating metastasis and also orchestrating immune evasion. Recent studies have found multiple evidences supporting the therapeutic potential of targeting CD24 in cancer treatment. Siglec-10, on the other hand, exhibits immunosuppressive properties that contribute to immune tolerance within the tumour microenvironment. Therefore, we delve into the complex mechanisms through which Siglec-10 modulates immune responses and facilitates immune escape in cancer. Siglec-10 also acts as a viable target for cancer immunotherapy and presents novel avenues for the development of therapeutic interventions. Furthermore, we examine the synergy between CD24 and Siglec-10 in shaping the immunosuppressive tumour microenvironment and discuss the implications for combination therapies. Therefore, understanding the roles of CD24 and Siglec-10 in cancer immunotherapy opens exciting possibilities for the development of novel therapeutics.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 3","pages":"442-469"},"PeriodicalIF":4.9,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916528","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":"Edwardsiella tarda induces airways inflammation and production of autoantibodies against lung tissues through regulation of the IL-33-ST2 axis","authors":"Yue Hu,&nbsp;Zhihong Feng,&nbsp;Gao An,&nbsp;Zhe Lv,&nbsp;Jingjing Wang,&nbsp;Ye Cui,&nbsp;Chris J. Corrigan,&nbsp;Wei Wang,&nbsp;Qin Li,&nbsp;Sun Ying","doi":"10.1111/imm.13848","DOIUrl":"10.1111/imm.13848","url":null,"abstract":"<p>Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic respiratory disease characterised by irreversible airways obstruction associated with chronic airways inflammation and remodelling, while the pathogenesis and the mechanistic differences between patients remain to be fully elucidated. We previously reported that alarmin cytokine IL-33 may contribute to the production of autoantibodies against respiratory epithelial cells. Here we expand the hypothesis that pulmonary autoimmune responses induced by airway microbiota also contribute to the progression of COPD. We focused on <i>Edwardsiella tarda</i> which we detected uniquely in the induced sputum of patients with acute exacerbations of COPD. Pernasal challenge of the airways of WT mice with supernatants of cultured <i>E. tarda</i> induced marked, elevated expression of IL-33 in the lung tissues. Immunisation of animals with supernatants of cultured <i>E. tarda</i> resulted in significantly elevated airways inflammation, the formation of tertiary lymphatic structures and significantly elevated proportions of T follicular helper T cells in the lung tissue and mediastinal lymph nodes. Interestingly, such challenge also induced production of IgG autoantibodies directed against lung tissue lysate, alveolar epithelial cell proteins and elastin fragment, while putrescine, one of metabolites generated by the bacterium, might play an important role in the autoantibody production. Furthermore, all of these effects were partly but significantly abrogated in mice with deletion of the IL-33 receptor ST2. Collectively, these data support the hypothesis that COPD is progressed at least partly by airways microbiota such as <i>E. tarda</i> initiating autoimmune attack of the airways epithelium mediated at least partly through the IL-33-ST2 axis.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 3","pages":"575-589"},"PeriodicalIF":4.9,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912463","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":"hnRNPs in antiviral innate immunity","authors":"Sofia Maceratessi,&nbsp;Natalia G. Sampaio","doi":"10.1111/imm.13846","DOIUrl":"10.1111/imm.13846","url":null,"abstract":"<p>During virus infection, many host proteins are redirected from their normal cellular roles to restrict and terminate infection. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are cellular RNA-binding proteins critical to host nucleic acid homeostasis, but can also be involved in the viral infection process, affecting virus replication, assembly and propagation. It has become evident that hnRNPs play important roles in modulation of host innate immunity, which provides critical initial protection against infection. These novel findings can potentially lead to the leveraging of hnRNPs in antiviral therapies. We review hnRNP involvement in antiviral innate immunity, in humans, mice and other animals, and discuss hnRNP targeting as a potential novel antiviral therapeutic.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 3","pages":"425-441"},"PeriodicalIF":4.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13846","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901535","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":"Dietary human milk oligosaccharides reduce allergic airway inflammation by modulating SCFAs level and ILC2 activity","authors":"Xu Han,&nbsp;Zhongjie Wang,&nbsp;Hongchuan Cao,&nbsp;Weiwei Liu,&nbsp;Lijie Sun,&nbsp;Qiang Xiao","doi":"10.1111/imm.13845","DOIUrl":"10.1111/imm.13845","url":null,"abstract":"<p>Group 2 innate lymphoid cells (ILC2s) play a crucial role in the progression of asthma, yet the regulatory mechanisms modulating ILC2 responses in asthma remain underexplored. Human milk oligosaccharides (HMOs), vital non-nutritive components of breast milk, are known to significantly shape immune system development and influence the incidence of allergic diseases. However, their impact on ILC2-driven asthma is not fully understood. Our research reveals that dietary HMOs act as potent inhibitors of ILC2 responses and allergic airway inflammation. Treatment with 2′-fucosyllactose (2'-FL) and 6′-sialyllactose (6'-SL) significantly reduced ILC2-related airway inflammation induced by papain or <i>Alternaria alternata</i> in mice, evidenced by decreased eosinophil (EOS) infiltration and lower IL-5 and IL-13 levels in BALF. Notably, while ILC2 expresses HMO receptors, HMO did not act directly on ILC2 but potentially modulated their activity through alterations in gut microbiota derived SCFAs. HMO treatments alleviated airway inflammation in SCFA-dependent manners, with SCFA depletion or receptor blocking reversing these beneficial effects. This study reveals the potential of dietary HMOs in managing asthma through modulation of ILC2 activity and the gut-lung axis, proposing a new therapeutic avenue that utilises the immunomodulatory capacities of nutritional components to combat respiratory diseases.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 3","pages":"562-574"},"PeriodicalIF":4.9,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897350","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":"Plonmarlimab, a novel anti-GM-CSF blocking antibody, ameliorates disease progression in the pre-clinical model of macrophage activation syndrome","authors":"Jian Ding,&nbsp;Ke Xu,&nbsp;Yanling Niu,&nbsp;Yihui Qin,&nbsp;Hong Shen,&nbsp;Yajuan Wang,&nbsp;Wenyu Guo,&nbsp;Xuejun Liu,&nbsp;Zhengyi Wang,&nbsp;Andrew X. Zhu","doi":"10.1111/imm.13842","DOIUrl":"10.1111/imm.13842","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We aimed to characterize and investigate the safety and efficacy of Plonmarlimab, a novel anti-granulocyte-macrophage colony-stimulating factor (anti-GM-CSF) neutralizing antibody, on the treatment of macrophage activation syndrome (MAS), a life-threatening systemic inflammatory disease, in pre-clinical models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The binding affinity was evaluated using Biacore. The neutralizing activity was measured through the blockade of ligand–receptor interaction, inhibition of STAT5 phosphorylation and suppression of TF-1 cell proliferation. The efficacy of Plonmarlimab was evaluated in a humanized MAS model, which was established by engrafting human umbilical cord blood (UCB) cells into NOG-EXL mice. Additionally, the safety profile of Plonmarlimab was investigated in cynomolgus monkeys.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At the molecular level, Plonmarlimab showed sub-nanomolar binding affinity with human GM-CSF and effectively blocked the binding of GM-CSF to its receptor. At the cellular level, Plonmarlimab dose-dependently inhibited intracellular STAT5 phosphorylation and suppressed GM-CSF-induced TF-1 proliferation. In the UCB-engrafted NOG-EXL MAS mouse model, Plonmarlimab treatment significantly ameliorated disease progression, demonstrated by the improvements in body weight loss, anaemia and some histopathological features. Furthermore, Plonmarlimab was well tolerated up to 150 mg/kg weekly in monkeys with no reported adverse effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Plonmarlimab is a highly potent GM-CSF blocking antibody and has demonstrated promising efficacy in a pre-clinical MAS model with a favourable safety profile, supporting its clinical development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 3","pages":"552-561"},"PeriodicalIF":4.9,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878650","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":"Spatial tertiary lymphoid structures imply response to anti-PD-1 plus anlotinib in advanced non-small cell lung cancer","authors":"Jianli Ma,&nbsp;Yuwei Deng,&nbsp;Minghui Zhang,&nbsp;Qingyuan Zhang","doi":"10.1111/imm.13841","DOIUrl":"10.1111/imm.13841","url":null,"abstract":"<p>Despite breakthroughs of immunotherapy synergistically combined with blockade of vascular endothelial growth factor receptor, several patients with advanced non-small cell lung cancer (NSCLC) experience non-response or followed relapse. Organized lymphoid aggregates, termed tertiary lymphoid structures (TLSs), are found to be associated with improved response to immunotherapy. Here, we explore the landscapes of TLSs in tumour tissues from a real-world retrospective study. Our investigation showed that with a median follow-up of 11.2 months, the ORR was 28.6% (18/63, 95% CI 17.9–41.3) and the median PFS was 6.1 (95% CI 5.5–6.6) months in NSCLC patients treated with PD-1 blockade combined with anlotinib. By multiplex immunofluorescence (mIF) analysis, spatially, more TLSs and high CD20+ B-cell ratio in TLSs were associated with higher ORR. High density of intratumoral CD8+ T cells showed better ORR and PFS. The numbers of CD8+ T cells with a distance within 20 μm and 20–50 μm between tumour cells were higher in responders than non-responders. But responders had significantly higher TLSs within 20 μm rather than within 20–50 μm of tumour cells than non-responders. The inflamed immunophenotyping occupied higher proportions in responders and was associated with better PFS. Besides, tumour cells in non-responders were found more temporal cell-in-cell structures than responders, which could protect inner cells from T-cell attacks. Taken together, landscape of TLSs and proximity architecture may imply superior responses to PD-1 blockade combined with anlotinib for patients with advanced non-small cell lung cancer.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 3","pages":"536-551"},"PeriodicalIF":4.9,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792453","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":"Fibroblast-like synoviocytes preferentially induce terminal differentiation of IgD+ memory B cells instead of naïve B cells","authors":"Dennis Bleck,&nbsp;Klara Loacker-Schöch,&nbsp;Tim Classen,&nbsp;Joachim Jose,&nbsp;Matthias Schneider,&nbsp;Georg Pongratz","doi":"10.1111/imm.13840","DOIUrl":"10.1111/imm.13840","url":null,"abstract":"<p>Rheumatoid arthritis (RA) is a systemic autoimmune disease driven by highly active autoantibody-producing B cells. Activation of B cells is maintained within ectopic germinal centres found in affected joints. Fibroblast-like synoviocytes (FLS) present in inflamed joints support B-cell survival, activation, and differentiation. CD27+ memory B cells and naive B cells show very different responses to activation, particularly by CD40 ligand (CD40L). We show that FLS-dependent activation of human B cells is dependent on interleukin-6 (IL-6) and CD40L. FLS have been shown to activate both naive and memory B cells. Whether the activating potential of FLS is different for naive and memory B cells has not been investigated. Our results suggest that FLS-induced activation of B cells is dependent on IL-6 and CD40L. While FLS are able to induce plasma cell differentiation, isotype switching, and antibody production in memory B cells, the ability of FLS to activate naive B cells is significantly lower.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 3","pages":"520-535"},"PeriodicalIF":4.9,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13840","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758482","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":"Hydroxychloroquine attenuates double-stranded RNA-stimulated hyper-phosphorylation of tristetraprolin/ZFP36 and AU-rich mRNA stabilization","authors":"Edward G. Hitti,&nbsp;Zeyad Muazzen,&nbsp;Walid Moghrabi,&nbsp;Suhad Al-Yahya,&nbsp;Khalid S. A. Khabar","doi":"10.1111/imm.13835","DOIUrl":"10.1111/imm.13835","url":null,"abstract":"<p>The human innate immune system recognizes dsRNA as a pathogen-associated molecular pattern that induces a potent inflammatory response. The primary source of pathogenic dsRNA is cells infected with replicating viruses, but can also be released from uninfected necrotic cells. Here, we show that the dsRNA poly(I:C) challenge in human macrophages activates the p38 MAPK-MK2 signalling pathway and subsequently the phosphorylation of tristetraprolin (TTP/ZFP36). The latter is an mRNA decay-promoting protein that controls the stability of AU-rich mRNAs (AREs) that code for many inflammatory mediators. Hydroxychloroquine (HCQ), a common anti-malaria drug, is used to treat inflammatory and autoimmune disorders and, controversially, during acute COVID-19 disease. We found that HCQ reduced the dsRNA-dependent phosphorylation of p38 MAPK and its downstream kinase MK2. Subsequently, HCQ reduced the abundance and protein stability of the inactive (phosphorylated) form of TTP. HCQ reduced the levels and the mRNA stability of poly (I:C)-induced cytokines and inflammatory mRNAs like TNF, IL-6, COX-2, and IL-8 in THP-1 and primary blood monocytes. Our results demonstrate a new mechanism of the anti-inflammatory role of HCQ at post-transcriptional level (TTP phosphorylation) in a model of dsRNA activation, which usually occurs in viral infections or RNA release from necrotic tissue.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 3","pages":"511-519"},"PeriodicalIF":4.9,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13835","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751607","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":"SOX17 orchestrates immune evasion in early colorectal adenomas and cancers","authors":"Bo Pei,&nbsp;Huiye Yang,&nbsp;Fuxiang Zhou","doi":"10.1111/imm.13831","DOIUrl":"10.1111/imm.13831","url":null,"abstract":"","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"422-424"},"PeriodicalIF":4.9,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748114","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":"Theories of immune recognition: Is anybody right?","authors":"Yuri Chaves Martins,&nbsp;Pamela Rosa-Gonçalves,&nbsp;Cláudio Tadeu Daniel-Ribeiro","doi":"10.1111/imm.13839","DOIUrl":"10.1111/imm.13839","url":null,"abstract":"<p>The clonal selection theory (CST) is the centrepiece of the current paradigm used to explain immune recognition and memory. Throughout the past decades, the original CST had been expanded and modified to explain new experimental evidences since its original publication by Burnet. This gave origin to new paradigms that govern experimental immunology nowadays, such as the associative recognition of antigen model and the stranger/danger signal model. However, these new theories also do not fully explain experimental findings such as natural autoimmune immunoglobulins, idiotypic networks, low and high dose tolerance, and dual-receptor T and B cells. To make sense of these empirical data, some authors have been trying to change the paradigm of immune cognition using a systemic approach, analogies with brain processing and concepts from second-order cybernetics. In the present paper, we review the CST and some of the theories/hypotheses derived from it, focusing on immune recognition. We point out their main weaknesses and highlight arguments made by their opponents and believers. We conclude that, until now, none of the proposed theories can fully explain the totality of immune phenomena and that a theory of everything is needed in immunology.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"274-285"},"PeriodicalIF":4.9,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13839","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733984","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}