Immunology最新文献

{"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}

{"title":"Peripheral blood MR1 tetramer-positive mucosal-associated invariant T-cell function is modulated by mammalian target of rapamycin complex 1 in patients with active tuberculosis","authors":"Chao-Ying Zhou,&nbsp;Ya-Long Yang,&nbsp;Zhen-Yu Han,&nbsp;Yao-Xin Chen,&nbsp;Hong-Lin Liu,&nbsp;Ke Fan,&nbsp;Ming-Chong Li,&nbsp;Si-Hang Tu,&nbsp;Qian Wen,&nbsp;Xin-Ying Zhou,&nbsp;Li Ma","doi":"10.1111/imm.13834","DOIUrl":"10.1111/imm.13834","url":null,"abstract":"<p>Tuberculosis (TB) is still an urgent global public health problem. Notably, mucosal-associated invariant T (MAIT) cells play an important role in early anti-TB immune response. Targeted control of them may be an effective method to improve vaccine efficacy and TB treatment. However, the biology and signal regulation mechanisms of MAIT cells in TB patients are still poorly understood. Previous studies have been limited by the lack of reagents to specifically identify MAIT cells. In addition, the use of alternative markers may subsume non-MAIT cell into MAIT cell populations. In this study, the human MR1 tetramer which can specifically identify MAIT cells was used to further explore the effect and mechanism of MAIT cells in anti-TB immune response. Our results showed that the tetramer⁺ MAIT cells in peripheral blood of TB patients were mainly CD8⁺ or CD4⁻CD8⁻ cells, and very few were CD4⁺ cells. After BCG infecting autologous antigen-presenting cells, MAIT cells in patients produced significantly higher levels of cytokines, lysis and proliferation compared with healthy controls. After suppression of mTORC1 by the mTORC1-specific inhibitor rapamycin, the immune response of MAIT cells in patients was significantly reduced. This study demonstrates that peripheral blood tetramer⁺ MAIT cells from TB patients have significant anti-TB immune effect, which is regulated by mTORC1. This could provide ideas and potential therapeutic targets for the development of novel anti-TB immunotherapy.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 3","pages":"497-510"},"PeriodicalIF":4.9,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13834","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633422","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":"NME4 suppresses NFκB2-CCL5 axis, restricting CD8+ T cell tumour infiltration in oesophageal squamous cell carcinoma","authors":"Shutao Zheng,&nbsp;Shuo He,&nbsp;Yan Liang,&nbsp;Qing Liu,&nbsp;Tao Liu,&nbsp;Yiyi Tan,&nbsp;Tianyuan Peng,&nbsp;Conggai Huang,&nbsp;Haidong Gao,&nbsp;Xiaomei Lu","doi":"10.1111/imm.13838","DOIUrl":"10.1111/imm.13838","url":null,"abstract":"<p>Thought of as a metastasis-associated gene, however, NME/NM23 nucleoside diphosphate kinase 4 (NME4) has rarely been described in the context of the tumour microenvironment. To understand the immunological implications of NME4 in oesophageal squamous cell carcinoma (ESCC), we used multiplex immunohistochemistry to analyse the clinicopathological and prognostic importance of NME4 expression. Then, after establishing a syngeneic tumour model with a C57BL/6 mouse strain that can recapitulate the tumour microenvironment of humans, we examined the immunological involvement of NME4 expression. To explore the underlying molecular mechanism, via quantitative proteomics and protein microarray screening, we investigated the potential signalling pathways involved. The clinicopathological and prognostic importance of NME4 expression is limited in ESCC patients. In vivo, single-cell RNA sequencing showed that NME4 strikingly prevented CD8+ T cells from infiltrating the tumour microenvironment in murine ESCC. Mechanistically, we mapped out the NFκB2-CCL5 axis that was negatively controlled by NME4 in the murine ESCC cell line AKR. Collectively, these data demonstrated that regulation of NFκB2-CCL5 axis by NME4 prevents CD8+ T cells infiltration in ESCC.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"408-421"},"PeriodicalIF":4.9,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626675","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}