Immunology & Cell Biology最新文献

{"title":"Mouse guanylate-binding protein 1 does not mediate antiviral activity against influenza virus in vitro or in vivo","authors":"Melkamu B Tessema,&nbsp;Daniel Enosi Tuipulotu,&nbsp;Clare V Oates,&nbsp;Andrew G Brooks,&nbsp;Si Ming Man,&nbsp;Sarah L Londrigan,&nbsp;Patrick C Reading","doi":"10.1111/imcb.12627","DOIUrl":"https://doi.org/10.1111/imcb.12627","url":null,"abstract":"<p>Many interferon (IFN)-stimulated genes are upregulated within host cells following infection with influenza and other viruses. While the antiviral activity of some IFN-stimulated genes, such as the IFN-inducible GTPase myxoma resistance (Mx)1 protein 1, has been well defined, less is known regarding the antiviral activities of related IFN-inducible GTPases of the guanylate-binding protein (GBP) family, particularly mouse GBPs, where mouse models can be used to assess their antiviral properties <i>in vivo</i>. Herein, we demonstrate that mouse GBP1 (mGBP1) was upregulated in a mouse airway epithelial cell line (LA-4 cells) following pretreatment with mouse IFNα or infection by influenza A virus (IAV). Whereas doxycycline-inducible expression of mouse Mx1 (mMx1) in LA-4 cells resulted in reduced susceptibility to IAV infection and reduced viral growth, inducible mGBP1 did not. Moreover, primary cells isolated from mGBP1-deficient mice (mGBP1^−/−) showed no difference in susceptibility to IAV and mGBP1^−/− macrophages showed no defect in IAV-induced NLRP3 (NLR family pyrin domain containing 3) inflammasome activation. After intranasal IAV infection, mGBP1^−/− mice also showed no differences in virus replication or induction of inflammatory responses in the airways during infection. Thus, using complementary approaches such as mGBP1 overexpression, cells from mGBP1^−/− mice and intranasal infection of mGBP1^−/− we demonstrate that mGBP1 does not play a major role in modulating IAV infection <i>in vitro</i> or <i>in vivo</i>.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"101 5","pages":"383-396"},"PeriodicalIF":4.0,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12627","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6114456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information","authors":"","doi":"10.1002/tesj.662","DOIUrl":"https://doi.org/10.1002/tesj.662","url":null,"abstract":"","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48711659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survey of activation-induced genome architecture reveals a novel enhancer of Myc","authors":"Wing Fuk Chan,&nbsp;Hannah D Coughlan,&nbsp;Michelle Ruhle,&nbsp;Nadia Iannarella,&nbsp;Carolina Alvarado,&nbsp;Joanna R Groom,&nbsp;Christine R Keenan,&nbsp;Andrew J Kueh,&nbsp;Adam K Wheatley,&nbsp;Gordon K Smyth,&nbsp;Rhys S Allan,&nbsp;Timothy M Johanson","doi":"10.1111/imcb.12626","DOIUrl":"https://doi.org/10.1111/imcb.12626","url":null,"abstract":"<p>The transcription factor Myc is critically important in driving cell proliferation, a function that is frequently dysregulated in cancer. To avoid this dysregulation Myc is tightly controlled by numerous layers of regulation. One such layer is the use of distal regulatory enhancers to drive <i>Myc</i> expression. Here, using chromosome conformation capture to examine B cells of the immune system in the first hours after their activation, we reveal a previously unidentified enhancer of <i>Myc</i>. The interactivity of this enhancer coincides with a dramatic, but discrete, spike in <i>Myc</i> expression 3 h post-activation. However, genetic deletion of this region, has little impact on <i>Myc</i> expression, Myc protein level or <i>in vitro</i> and <i>in vivo</i> cell proliferation. Examination of the enhancer deleted regulatory landscape suggests that enhancer redundancy likely sustains <i>Myc</i> expression. This work highlights not only the importance of temporally examining enhancers, but also the complexity and dynamics of the regulation of critical genes such as <i>Myc</i>.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"101 4","pages":"345-357"},"PeriodicalIF":4.0,"publicationDate":"2023-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12626","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5876108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Semliki Forest virus encephalitis, suppressor of cytokine signaling 4 (SOCS4) is an essential modulator of immune responses that mediates the balance between immunopathology and virus clearance","authors":"Lukasz Kedzierski,&nbsp;Abigail Er Qi Tan,&nbsp;Isabelle Jia Hui Foo,&nbsp;Divya Narayanan,&nbsp;Nagaraj Moily,&nbsp;Hayley A McQuilten,&nbsp;Sandra E Nicholson,&nbsp;John K Fazakerley","doi":"10.1111/imcb.12625","DOIUrl":"https://doi.org/10.1111/imcb.12625","url":null,"abstract":"<p>Central nervous system virus infections are a major cause of morbidity and mortality worldwide and a significant global public health concern. As in many tissues, inflammation and immune responses in the brain, despite their protective roles, can also be harmful. Control of brain inflammation is important in many neurological diseases from encephalitis to multiple sclerosis and neurogenerative disease. The suppressors of cytokine signaling (SOCS) proteins are a key mechanism controlling inflammatory and immune responses across all tissues including the brain. Using a mouse model system, we demonstrate that lack of SOCS4 results in changes in the pathogenesis and clinical outcome of a neurotropic virus infection. Relative to wild-type mice, SOCS4-deficient mice showed accelerated clearance of virus from the brain, lower levels of persisting viral RNA in the brain, increased neuroinflammation and more severe neuropathology. We conclude that, in the mouse brain, SOCS4 is a vital regulator of antiviral immunity that mediates the critical balance between immunopathology and virus persistence.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"101 4","pages":"333-344"},"PeriodicalIF":4.0,"publicationDate":"2023-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12625","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5805980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green Labs: a guide to developing sustainable science in your organization","authors":"Joanne Durgan,&nbsp;Marta Rodríguez-Martínez,&nbsp;Brendan Rouse","doi":"10.1111/imcb.12624","DOIUrl":"https://doi.org/10.1111/imcb.12624","url":null,"abstract":"<p>Scientific research plays a vital role for society, but carries a significant environmental footprint, involving intensive use of energy and resources. Scientists are well placed to understand the unfolding climate and ecological crises, but may not appreciate how heavily their research, and other work-related activities, contribute to emissions and pollution. With the consequences of climate change and ecological breakdown playing out in real time, scientists now have an important, urgent role to play in catalyzing solutions. Here, we explore how research organizations can reduce their environmental impact, share useful resources and encourage the global community to engage in making science more sustainable.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"101 4","pages":"289-301"},"PeriodicalIF":4.0,"publicationDate":"2023-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12624","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5818435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating effector γδ T cell populations are associated with acute coronavirus disease 19 in unvaccinated individuals","authors":"Anouk von Borstel,&nbsp;Thi HO Nguyen,&nbsp;Louise C Rowntree,&nbsp;Thomas M Ashhurst,&nbsp;Lilith F Allen,&nbsp;Lauren J Howson,&nbsp;Natasha E Holmes,&nbsp;Olivia C Smibert,&nbsp;Jason A Trubiano,&nbsp;Claire L Gordon,&nbsp;Allen C Cheng,&nbsp;Stephen J Kent,&nbsp;Jamie Rossjohn,&nbsp;Katherine Kedzierska,&nbsp;Martin S Davey","doi":"10.1111/imcb.12623","DOIUrl":"https://doi.org/10.1111/imcb.12623","url":null,"abstract":"<p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe coronavirus disease 2019 (COVID-19) in a small proportion of infected individuals. The immune system plays an important role in the defense against SARS-CoV-2, but our understanding of the cellular immune parameters that contribute to severe COVID-19 disease is incomplete. Here, we show that populations of effector γδ T cells are associated with COVID-19 in unvaccinated patients with acute disease. We found that circulating CD27^negCD45RA⁺CX3CR1⁺ Vδ1_effector cells expressing Granzymes (Gzms) were enriched in COVID-19 patients with acute disease. Moreover, higher frequencies of GzmB⁺ Vδ2⁺ T cells were observed in acute COVID-19 patients. SARS-CoV-2 infection did not alter the γδ T cell receptor repertoire of either Vδ1⁺ or Vδ2⁺ subsets. Our work demonstrates an association between effector populations of γδ T cells and acute COVID-19 in unvaccinated individuals.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"101 4","pages":"321-332"},"PeriodicalIF":4.0,"publicationDate":"2023-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12623","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5818441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ataxin-1 controls the expression of specific noncoding RNAs in B cells upon autoimmune demyelination","authors":"Qin Ma,&nbsp;Alessandro Didonna","doi":"10.1111/imcb.12622","DOIUrl":"https://doi.org/10.1111/imcb.12622","url":null,"abstract":"<p>B cells play a key mechanistic role in the pathogenesis of multiple sclerosis (MS), a chronic neurological disease of the central nervous system with an autoimmune etiology. B cells contribute to disease initiation and progression by acting as professional antigen-presenting cells as well as <i>via</i> secreting autoantibodies and proinflammatory cytokines. We have recently shown that the polyglutamine protein ataxin-1, which was first linked to the movement disorder spinocerebellar ataxia type 1, also acts as a master regulator of B-cell functions in the context of central nervous system autoimmunity. In fact, ataxin-1–deficient mice display an aggravated manifestation of the MS disease model experimental autoimmune encephalomyelitis along with aberrant B-cell functions. Consistent with this scenario, transcriptomic analysis of <i>Atxn1</i>-null B cells highlighted distinct genetic signatures involved in cell activation, proliferation and antigen presentation. To further characterize the role of ataxin-1, we profiled the noncoding transcriptome controlled by ataxin-1 in the B-cell compartment upon an encephalitogenic challenge. We show that two specific classes of noncoding RNAs, namely, processed pseudogenes and intergenic long noncoding RNAs, are differentially regulated along disease. Furthermore, pathway and protein network analyses on their putative protein-coding gene targets found a significant enrichment in ontologies related to cell mitosis, together with molecular processes relevant to MS such as chitin metabolism. Altogether, these findings shed light on the possible contribution of noncoding RNAs to B-cell biology and MS pathogenesis, and further establish the immunomodulatory role of ataxin-1 in autoimmune demyelination.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"101 4","pages":"358-367"},"PeriodicalIF":4.0,"publicationDate":"2023-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12622","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5980844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection","authors":"Yee Teng Chan,&nbsp;Yi Ying Cheok,&nbsp;Heng Choon Cheong,&nbsp;Grace Min Yi Tan,&nbsp;Shi Rui Seow,&nbsp;Ting Fang Tang,&nbsp;Sofiah Sulaiman,&nbsp;Chung Yeng Looi,&nbsp;Rishein Gupta,&nbsp;Bernard Arulanandam,&nbsp;Won Fen Wong","doi":"10.1111/imcb.12621","DOIUrl":"https://doi.org/10.1111/imcb.12621","url":null,"abstract":"<p>Genital <i>Chlamydia trachomatis</i> infection remains a major health issue as it causes severe complications including pelvic inflammatory disease, ectopic pregnancy and infertility in females as a result of infection-associated chronic inflammation. Podoplanin, a transmembrane receptor, has been previously reported on inflammatory macrophages. Thus, strategies that specifically target podoplanin might be able to reduce local inflammation. This study investigated the expression level and function of podoplanin in a <i>C. trachomatis</i> infection model. C57BL/6 mice infected with the mouse pathogen <i>Chlamydia muridarum</i> were examined intermittently from days 1 to 60 using flow cytometry analysis. Percentages of conventional macrophages (CD11b⁺CD11c⁻F4/80⁺) <i>versus</i> inflammatory macrophages (CD11b⁺CD11c⁺F4/80⁺), and the expression of podoplanin in these cells were investigated. Subsequently, a podoplanin-knockout RAW264.7 cell was used to evaluate the function of podoplanin in <i>C. trachomatis</i> infection. Our findings demonstrated an increased CD11b⁺ cell volume in the spleen at day 9 after the infection, with augmented podoplanin expression, especially among the inflammatory macrophages. A large number of podoplanin-expressing macrophages were detected in the genital tract of <i>C. muridarum</i>–infected mice. Furthermore, analysis of the <i>C. trachomatis</i>–infected patients demonstrated a higher percentage of podoplanin-expressing monocytes than that in the noninfected controls. Using an <i>in vitro</i> infection in a transwell migration assay, we identified that macrophages deficient in podoplanin displayed defective migratory function toward <i>C. trachomatis</i>–infected HeLa 229 cells. Lastly, using immunoprecipitation–mass spectrometry method, we identified two potential podoplanin interacting proteins, namely, Cofilin 1 and Talin 1 actin-binding proteins. The present study reports a role of podoplanin in directing macrophage migration to the chlamydial infection site. Our results suggest a potential for reducing inflammation in individuals with chronic chlamydial infections by targeting podoplanin.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"101 4","pages":"305-320"},"PeriodicalIF":4.0,"publicationDate":"2023-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5928537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The regulation of N6-methyladenosine modification in PD-L1-induced anti-tumor immunity","authors":"Wei Yu,&nbsp;Jinti Lin,&nbsp;Tao Yu,&nbsp;Jianan Lou,&nbsp;Chao Qian,&nbsp;Ankai Xu,&nbsp;Bing Liu,&nbsp;Huimin Tao,&nbsp;Libin Jin","doi":"10.1111/imcb.12620","DOIUrl":"https://doi.org/10.1111/imcb.12620","url":null,"abstract":"<p>There is growing evidence that programmed death ligand-1 (PD-L1) has exciting therapeutic efficacy in hematological malignancy and partial solid tumors. However, many patients still face failure with the treatment of immune checkpoint blockade because of PD-L1 expression regulation during transcription and post-transcription processes, including N6-methyladenosine (m6A). Similar to the epigenetic regulation in DNA and histones, recent research has revealed the essential regulation of m6A modification in RNA nuclear export, metabolism and translation. Recent studies have shown that m6A-induced PD-L1 expression emerges as one of the main reasons for the immunological alteration in this process and contributes to the failure of T cell-induced anti-tumor immunity. The results of preclinical studies demonstrate the potential of m6A-targeted therapy in combination with immune checkpoint blockade. The comprehensive expression of m6A-related genes also provided the possibility to indicate the prognosis and to optimize the treatment for patients of various cancer types. In this review, we focus on the m6A modification in PD-L1 mRNA as well as the regulation of PD-L1 expression in cancer cells and summarize its clinical value in anti-PD-L1 cancer immune therapy.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"101 3","pages":"204-215"},"PeriodicalIF":4.0,"publicationDate":"2023-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12620","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6090045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal analysis of mucosa-associated invariant T cells in sepsis reveals their early numerical decline with prognostic implications and a progressive loss of antimicrobial functions","authors":"Joshua Choi,&nbsp;Crystal L Schmerk,&nbsp;Tina S Mele,&nbsp;Patrick T Rudak,&nbsp;Christine M Wardell,&nbsp;Gansen Deng,&nbsp;Farzan R Pavri,&nbsp;Kyoungok Kim,&nbsp;Gediminas Cepinskas,&nbsp;Wenqing He,&nbsp;SM Mansour Haeryfar","doi":"10.1111/imcb.12619","DOIUrl":"https://doi.org/10.1111/imcb.12619","url":null,"abstract":"<p>Sepsis-elicited immunosuppression elevates the risk of secondary infections. We used a clinically relevant mouse model and serial peripheral blood samples from patients to assess the antimicrobial activities of mucosa-associated invariant T (MAIT) cells in sepsis. Hepatic and splenic MAIT cells from B6-MAIT^CAST mice displayed increased CD69 expression and a robust interferon-γ (IFNγ) production capacity shortly after sublethal cecal ligation and puncture, but not at a late timepoint. Peripheral blood MAIT cell frequencies were reduced in septic patients at the time of intensive care unit (ICU) admission, and more dramatically so among nonsurvivors, suggesting the predictive usefulness of early MAIT cell enumeration. In addition, at ICU admission, MAIT cells from sepsis survivors launched stronger IFNγ responses to several bacterial species compared with those from patients who subsequently died of sepsis. Of note, while low human leukocyte antigen (HLA)-DR⁺ monocyte frequencies, widely regarded as a surrogate indicator of sepsis-induced immunosuppression, were gradually corrected, the numerical insufficiency of MAIT cells was not resolved over time, and their CD69 expression continued to decline. MAIT cell responses to bacterial pathogens, a major histocompatibility complex–related protein 1 (MR1) ligand, and interleukin (IL)-12 and IL-18 were also progressively lost during sepsis and did not recover by the time of ICU/hospital discharge. We propose that MAIT cell dysfunctions contribute to post-sepsis immunosuppression.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"101 3","pages":"249-261"},"PeriodicalIF":4.0,"publicationDate":"2023-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12619","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5713429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}