Current Opinion in Immunology最新文献

{"title":"Mechanistic considerations linking SARS-CoV-2 infection, inflammation, and the loss of immune tolerance","authors":"Antonio Tonutti ,&nbsp;Francesca Motta ,&nbsp;Natasa Isailovic ,&nbsp;Carlo Selmi ,&nbsp;Suraj Timilsina ,&nbsp;Merrill Eric Gershwin ,&nbsp;Maria De Santis","doi":"10.1016/j.coi.2025.102567","DOIUrl":"10.1016/j.coi.2025.102567","url":null,"abstract":"<div><div>The immune response to SARS-CoV-2 has been implicated in the onset of multiple, seemingly unrelated, autoimmune diseases. The immune response to SARS-CoV-2 has also been implicated in the unmasking and/or production of multiple autoantibodies, even in the absence of clinical disease. Despite such data, it remains unclear whether antibodies targeting antiviral signaling proteins and mitochondrial antigens reflect bystander activation or alternatively contribute to <em>de novo</em> viral immune escape mechanisms. With these comments in mind, a variety of professional antibody presenting cells and including lung resident macrophages of COVID-19 infected patients are impacted and dependent on the uptake of antibody-opsonized virus by Fcγ receptors; yet infection is aborted via antibody-dependent effector mechanisms or pyroptosis, possibly leading to autoantibody production, and autoinflammatory manifestations, respectively.</div><div>TRIM21/Ro52, a cytosolic E3-ubiquitin ligase with an Fc-gamma receptor domain, functions as an intracytoplasmic antibody receptor, directs immune complexes binding virions but also autoantigens to autophagy. During autophagy, Ig-virions-TRIM21/Ro52-autoantigens complexes bind directly to class II human leukocyte antigen in lysosomal compartment, leading to subsequent presentation on the cell surface. This process favors the development of a specific humoral immune response but has the potential to lead to loss of tolerance. Interestingly, TRIM21/Ro52 can also contribute to pyroptosis. We propose that TRIM21/Ro52 is well-placed at the crossroad between the inflammatory response and clinical autoimmunity.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"95 ","pages":"Article 102567"},"PeriodicalIF":6.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"‘Can we cure IgG4-related diseases?’","authors":"Kazuichi Okazaki ,&nbsp;Tsukasa Ikeura ,&nbsp;Kazushige Uchida","doi":"10.1016/j.coi.2025.102564","DOIUrl":"10.1016/j.coi.2025.102564","url":null,"abstract":"<div><div>IgG4-related disease (IgG4-RD), recognized as a novel clinical entity, is a rare, chronic, immune-mediated systemic fibroinflammatory disorder of unknown origin with either synchronous or metachronous multi-organ involvement. Although the pathogenic mechanism remains unclear, possible multipathogenic factors such as genetic backgrounds, disease-specific or related antigens, and abnormal innate or adaptive immunity may be involved. Many immunocytes, including neutrophil extracellular trap, M2 macrophage, plasmablast, B cells, and T-cells (Th2-CD4⁺T, follicular helper T cells, and CD4⁺SLAMF7⁺cytotoxic T cells) play important roles in the pathogenesis. Conventional therapies with glucocorticoid or rituximab in combination with/without immunomodulators are recommended in all symptomatic patients with active IgG4-RD. Because of a few of randomized clinical trials, the comprehensive management for IgG4-RD has not been established yet. Targeted treatment approaches against the plasmablast to B cell lineage and the CD4⁺SLAMF7⁺cytotoxic T cell seem to be promising for the future-directed treatment.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"95 ","pages":"Article 102564"},"PeriodicalIF":6.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2: lessons in virus mutation prediction and pandemic preparedness","authors":"Weiyi Tang ,&nbsp;Jenna Kim ,&nbsp;Raphael TC Lee ,&nbsp;Sebastian Maurer-Stroh ,&nbsp;Laurent Renia ,&nbsp;Matthew Z Tay","doi":"10.1016/j.coi.2025.102560","DOIUrl":"10.1016/j.coi.2025.102560","url":null,"abstract":"<div><div>The COVID-19 pandemic has prompted an unprecedented global response. In particular, extraordinary efforts have been dedicated toward monitoring and predicting variant emergence due to its huge impact, particularly for vaccine escape. Broadly, we classify such methods into two categories: forward mutation prediction, where phenotypes are first observed and the responsible genotypes traced, and reverse mutation prediction, which starts with selected pathogen genetic profiles and characterizes their associated phenotypes. Reverse mutation prediction strategies have advantages in being able to sample a more complete evolutionary space since sequences that do not yet exist can be sampled. The rapid improvement in the maturity and scale of reverse mutation prediction strategies, such as deep mutational scanning, has led to significant amounts of data for machine learning, with concomitant improvement in the prediction results from computational tools. Such integrated prediction approaches are generalizable and offer significant opportunities for anticipating viral evolution and for pandemic preparedness.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"95 ","pages":"Article 102560"},"PeriodicalIF":6.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can we cure rheumatoid arthritis?","authors":"Yi Yin ,&nbsp;Meiyu Guo ,&nbsp;Peter E Lipsky ,&nbsp;Xuan Zhang","doi":"10.1016/j.coi.2025.102561","DOIUrl":"10.1016/j.coi.2025.102561","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) persists as a chronically progressive autoimmune disorder, notwithstanding significant advancements in early intervention and precision-targeted therapeutics. While treat-to-target paradigms and disease-modifying antirheumatic drugs ameliorate clinical outcomes, sustained drug-free remission (SDFR) or even cure remains elusive, underscoring the need for innovative strategies addressing underlying immunopathogenic mechanisms. Prolonged SDFR implies cure or eradication of disease, but there is no consensus definition of cure because it has rarely been contemplated in RA. Pathogenic immune circuit resilience, stromal hyperactivation, persistent structural abnormalities, and genetic susceptibilities constitute multifactorial barriers to a cure. Emerging therapies — including novel biologics, cellular interventions, and gene editing — aim to reprogram pathogenic immune responses rather than suppress symptoms and may have the potential for both SDFR and possibly cure. Whereas preclinical and early clinical data suggest the potential to modify disease trajectories, durable resetting of the RA immune system toward normal has not yet been conclusively demonstrated or uniformly achieved in RA. The ‘window of opportunity’ paradigm postulates that early-stage immunomodulatory interventions may alter the disease trajectory. However, the optimal therapeutic approaches for capitalizing on this temporal window remain debated, particularly regarding the integration of personalized biomarkers and mechanistic targets.</div><div>This review summarizes advancements in RA therapeutics, evaluating whether emerging modalities can pivot the clinical paradigm from symptomatic management to the induction of persistent immunological normalization and cure. Although definitive cure remains on the far horizon, the rapid convergence of precision medicine, next-generation immunotherapy, and translational research underscores a paradigm shift toward curative strategies.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102561"},"PeriodicalIF":6.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological insights into the re-emergence of human metapneumovirus","authors":"Arpan Acharya,&nbsp;Siddappa N Byrareddy","doi":"10.1016/j.coi.2025.102562","DOIUrl":"10.1016/j.coi.2025.102562","url":null,"abstract":"<div><div>Human metapneumovirus (hMPV) is a seasonal respiratory virus that typically causes mild, flu-like symptoms. In some cases, it can lead to severe respiratory complications, such as pneumonia, bronchitis, and bronchiolitis, often requiring hospitalization. Recently, a surge in hMPV cases has been reported in China and other countries, raising concerns about a potential pandemic scenario reminiscent of COVID-19. This review explores the genomic structure, replication cycle, genetic diversity, and evolutionary trajectory of hMPV. It also discusses host immune responses and the available animal models to study pathogenesis and to screen for potential vaccines and antivirals. Additionally, we examine the shifting seasonal trends in hMPV circulation, evaluate the low pandemic risk posed by existing hMPV clades, and underscore the need for continued vaccine and antiviral development. Finally, we advocate for strengthened global surveillance, especially in low- and middle-income countries, as a critical strategy to mitigate the risks posed by emerging hMPV clades.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102562"},"PeriodicalIF":6.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dupilumab-associated lymphoproliferative disorders: a comprehensive review on clinicohistopathologic features and underlying mechanisms","authors":"Mingjia Li ,&nbsp;Wei Zhao ,&nbsp;Pan Lai ,&nbsp;Yu Xiao ,&nbsp;Yang Wang","doi":"10.1016/j.coi.2025.102563","DOIUrl":"10.1016/j.coi.2025.102563","url":null,"abstract":"<div><div>Dupilumab, a monoclonal antibody targeting interleukin 4 receptor, has shown significant efficacy in treating atopic dermatitis (AD). However, emerging case reports indicate that it may unmask or cause cutaneous T cell lymphoma (CTCL). This review analyzes 29 studies involving 124 patients who developed lymphoproliferative disorders after dupilumab, including 13 cases of lymphoproliferative reactions not meeting lymphoma criteria.</div><div>The median time from dupilumab initiation to biopsy-confirmed lymphoproliferative disorders was 5 months, with 39.05% of cases in advanced stages. Histopathological examination of dupilumab-induced CTCL reveals epidermotropism with spongiosis and increased superficial lymphoid infiltration. Notably, early lymphoproliferative reaction shows subtle lymphoma features, characterized by perivascular infiltration with sprinkled intraepidermal lymphocytes, CD30 expression, and absence of clonal TCR rearrangement and T-cell markers loss. Adult-onset AD patients, particularly those with atypical skin lesions, short-term exacerbation, or no atopy history, should be closely monitored during dupilumab treatment, and skin biopsy is essential if no clinical improvement occurs. Discontinuation is recommended when lymphoid infiltration increases, even without typical lymphoma features.</div><div>The mechanisms underlying dupilumab-associated lymphoma remain speculative. Current hypotheses include upregulation of IL13RA2 signaling pathway, prolonged persistence of immune cell populations, and varying responses of different tumor cell subclusters. Additionally, the effects of dupilumab on various cell types are complex and multifaceted. Consequently, the distribution of type 2 inflammatory cytokine receptors and the patterns of cellular infiltration within the microenvironment may impact disease progression following dupilumab treatment. Further research is needed to clarify the mechanisms linking dupilumab to CTCL for better defining dupilumab's safety profile.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102563"},"PeriodicalIF":6.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in genetic–immunological targeted therapies for psoriasis","authors":"Qi Zhen ,&nbsp;Yirui Wang ,&nbsp;Zhuo Li ,&nbsp;Liangdan Sun","doi":"10.1016/j.coi.2025.102559","DOIUrl":"10.1016/j.coi.2025.102559","url":null,"abstract":"<div><div>Psoriasis is a common chronic immune-mediated inflammatory skin disease, with its pathogenesis involving genetic susceptibility, abnormal immune responses, and environmental factors. In recent years, targeted immunotherapy has become a prominent treatment approach. Various drugs targeting cytokines, such as interleukin-17, interleukin-23, and tumor necrosis factor-α, have been introduced, effectively alleviating symptoms. However, due to the complex immunopathogenesis of psoriasis and individual patient differences, single-target drugs may not consistently provide comprehensive treatment effects. Therefore, this article suggests that future research should prioritize multitarget combination therapies to enhance efficacy and reduce resistance. Personalized treatment strategies, based on patients’ genetic, immune, and clinical characteristics, should be developed. Investigating new immunomodulatory mechanisms and drugs, as well as combination therapies that integrate targeted drugs with phototherapy or cellular therapy, is also crucial. Additionally, exploring long-term efficacy and resistance mechanisms will help improve treatment outcomes, with the goal of transforming psoriasis treatment.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102559"},"PeriodicalIF":6.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoimmunity in inflammatory bowel disease: a holobiont perspective","authors":"Henry Taylor ,&nbsp;Holm H Uhlig ,&nbsp;Fiona Powrie","doi":"10.1016/j.coi.2025.102557","DOIUrl":"10.1016/j.coi.2025.102557","url":null,"abstract":"<div><div>Adaptive immunity towards self-antigens (autoimmunity) and intestinal commensal microbiota is a key feature of inflammatory bowel disease (IBD). Considering mucosal adaptive immunity from a holobiont perspective, where the host and its microbiome form a single physiological unit, emphasises the challenge of avoiding damaging responses to self-antigen and symbiotic microbial communities in the gut while protecting against potential pathogens. Intestinal tolerance mechanisms prevent maladaptive T and B cell responses to microbial, environmental, and self-antigens, which drive inflammation. We discuss the spectrum of antimicrobial and autoantibody responses and highlight mechanisms by which common IBD-associated adaptive immune responses contribute to disease.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102557"},"PeriodicalIF":6.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drivers and shapers of macrophages specification in the developing brain","authors":"Simone Brioschi ,&nbsp;Claudia Z Han ,&nbsp;Marco Colonna","doi":"10.1016/j.coi.2025.102558","DOIUrl":"10.1016/j.coi.2025.102558","url":null,"abstract":"<div><div>The brain harbors two major macrophage populations: microglia reside within the brain parenchyma, while border-associated macrophages (BAMs) are situated at central nervous system (CNS) interfaces. BAMs can be further classified into distinct subsets based on their localization: perivascular macrophages surround blood vessels, meningeal macrophages reside in the leptomeninges, dura macrophages in the dura mater, and choroid plexus macrophages are confined to the choroid plexus. The environmental factors and molecular mechanisms driving the specification of these macrophage populations are still being elucidated. Deciphering the communication pathways between CNS macrophages and their tissue niches during development, homeostasis, and pathologic conditions offers significant potential for treating a wide range of brain disorders, from neurodevelopmental and neuroinflammatory diseases to neurovascular and neurodegenerative conditions. With this short review, we will address the current understanding and knowledge gaps in the field, as well as the future directions for the upcoming years.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102558"},"PeriodicalIF":6.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoimmune-related adverse events induced by immune checkpoint inhibitors","authors":"Yuanqiang Sun ,&nbsp;Ziyang Zhang ,&nbsp;Ke Jia ,&nbsp;Hong Liu ,&nbsp;Furen Zhang","doi":"10.1016/j.coi.2025.102556","DOIUrl":"10.1016/j.coi.2025.102556","url":null,"abstract":"<div><div>Targeted immunotherapies, particularly immune checkpoint inhibitors (ICIs), have transformed cancer treatment by significantly improving patient response and survival rates. However, ICIs could disrupt self-tolerance, inducing the development of immune-related adverse events (irAEs). Most irAEs are classified as autoimmune conditions mediated by ICI-activated CD8+ cytotoxic T cells or activated B cells producing pathogenic autoantibodies. These irAEs phenotypically resemble spontaneous autoimmune disease and lead to considerable morbidity, health care costs, and compromised treatment efficacy. With the widespread use and new emergence of ICIs, the spectrum of ICI-induced irAEs has become increasingly extensive and complex. Concurrently, research in this field is advancing rapidly, a review summarizing the latest progress on irAEs is timely and essential. In this review, we highlight numerous recent research advances, covering the epidemiology, immune mechanisms, and diverse manifestations of irAEs, with a particular focus on organ-specific autoimmunity. We also discuss current strategies, challenges, and future directions for the prevention and therapeutic management of these adverse events.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"94 ","pages":"Article 102556"},"PeriodicalIF":6.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}