Seminars in Immunology最新文献

{"title":"The role of the adaptive immune system in the initiation and persistence of multiple sclerosis","authors":"Ali Maisam Afzali ,&nbsp;Thomas Korn","doi":"10.1016/j.smim.2025.101947","DOIUrl":"10.1016/j.smim.2025.101947","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) in which complex networks of interacting immune cells initiate and sustain the disease. The pathogenesis of relapsing MS is driven by adaptive immune cells that become activated outside the CNS compartment and then migrate into the CNS to initiate a presumably autoimmune inflammatory process. Recent technological advances, particularly single-cell analyses, have revealed substantial heterogeneity in T and B cells involved in this stage of the disease. Disease progression involves different mechanisms, with compartmentalized inflammation and chronic activation of CNS-resident cells becoming predominant features. The contribution of tissue-resident adaptive immune cells to the pathology of progressive MS, including tissue-resident CD8⁺ T cells and B cells in the meningeal compart, is increasingly debated. Here, we will discuss concepts of how adaptive immune cells might initiate and maintain autoimmune inflammation in the CNS, while the responses to autoimmune inflammation of CNS intrinsic cells, including astrocytes, oligodendrocytes, and neurons, are described elsewhere <span><span>[1]</span></span>, <span><span>[2]</span></span>, <span><span>[3]</span></span>, <span><span>[4]</span></span>, <span><span>[5]</span></span> and will not be a particular focus of this overview. Finally, it is the aim of this review to conceptualize the grounds for efficient therapeutic interventions targeting players of the adaptive immune system in relapsing but also in progressive MS.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101947"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune dysregulation of diabetes in tuberculosis","authors":"Pei Min Thong ,&nbsp;Yi Hao Wong ,&nbsp;Hardy Kornfeld ,&nbsp;Delia Goletti ,&nbsp;Catherine W.M. Ong","doi":"10.1016/j.smim.2025.101959","DOIUrl":"10.1016/j.smim.2025.101959","url":null,"abstract":"<div><div>The rising prevalence of diabetes mellitus (DM) is undermining global efforts to eliminate tuberculosis (TB). Most studies found that patients with pulmonary TB and DM have more cavitary lung lesions, higher mycobacterial burden on the lungs, longer periods of infectiousness, and worse outcomes. Both human and animal studies indicate that TB-DM is associated with impaired innate and adaptive immune responses, resulting in delayed bacterial clearance. Similar observations have been noted in other infections, such as those caused by <em>Klebsiella pneumoniae</em>, where DM contributes to increased susceptibility and worse outcomes due to compromised immune functions including defective phagocytosis and impaired early immune cell recruitment. This review delves into the mechanisms of immune dysfunction in TB-DM, exploring how DM increases TB susceptibility and severity. By elucidating these complex interactions, this review aims to offer insights into more effective strategies for managing and improving outcomes for patients with this challenging comorbidity.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101959"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855100","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":"The pathogenesis of neurological immune-related adverse events following immune checkpoint inhibitor therapy","authors":"Magdalena Lerch ,&nbsp;Sudarshini Ramanathan","doi":"10.1016/j.smim.2025.101956","DOIUrl":"10.1016/j.smim.2025.101956","url":null,"abstract":"<div><div>Cancer is a leading cause of morbidity and mortality worldwide. The development of immune checkpoint inhibitors (ICI) has revolutionised cancer therapy, and patients who were previously incurable can now have excellent responses. These therapies work by blocking inhibitory immune pathways, like cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death-1 (PD-1), its ligand PD-L1, and lymphocyte activation gene 3 (LAG-3); which leads to increased anti-tumour immune responses. However, their use can lead to the development of immune-related adverse events (irAEs), which may result in severe disability, interruption of cancer therapy, and even death. Neurological autoimmune sequelae occur in 1–10 % of patients treated with ICIs and can be fatal. They encompass a broad spectrum of diseases, may affect the central and the peripheral nervous system, and include syndromes like encephalitis, cerebellitis, neuropathy, and myositis. In some cases, neurological irAEs can be associated with autoantibodies recognising neuronal or glial targets. In this review, we first describe the key targets in ICI therapy, followed by a formulation of irAEs and their clinical presentations, where we focus on neurological syndromes. We comprehensively formulate the current literature evaluating cell surface and intracellular autoantibodies, cytokines, chemokines, leukocyte patterns, other blood derived biomarkers, and immunogenetic profiles; and highlight their impact on our understanding of the pathogenesis of neurological irAEs. Finally, we describe therapeutic pathways and patient outcomes, and provide an overview on future aspects of ICI cancer therapy.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101956"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877450","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":"The immunological processes behind aquaporin 4-antibody seropositive neuromyelitis optica spectrum disorders","authors":"Monika Bradl ,&nbsp;Qian Yu ,&nbsp;Yoshiki Takai","doi":"10.1016/j.smim.2025.101945","DOIUrl":"10.1016/j.smim.2025.101945","url":null,"abstract":"<div><div>Ever since the discovery of pathogenic aquaporin 4-specific antibodies in the serum of patients with neuromyelitis optica spectrum disorders current knowledge about clinical observations and diagnosis, and about the underlying pathology and resulting therapies have been put forward in excellent reviews and primary publications. However, in order to further develop novel strategies for the treatment of this disease, there is an urgent need to understand the immunological processes associated with the formation of the pathogenic antibodies, and with aberrant immune responses observed in affected patients. In this review, we will highlight and evaluate important studies on these processes.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101945"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From immunobiology to intervention: Pathophysiology of autoimmune encephalitis","authors":"Marie A. Homeyer ,&nbsp;Alice Falck ,&nbsp;Lucie Y. Li ,&nbsp;Harald Prüss","doi":"10.1016/j.smim.2025.101955","DOIUrl":"10.1016/j.smim.2025.101955","url":null,"abstract":"<div><div>Autoimmune encephalitides (AEs) are neurological disorders caused by autoantibodies against neuronal and glial surface proteins. Nearly 20 years after their discovery, AE have evolved from being frequently misdiagnosed and untreated to a growing group of increasingly well-characterized conditions where patients benefit from targeted therapeutic strategies. This narrative review provides an immunological perspective on AE, focusing on NMDAR, CASPR2 and LGI1 encephalitis as the three most common forms of AE associated with anti-neuronal surface autoantibodies. We examine the autoreactive B cell subsets, the tolerance checkpoints that may fail, and the known triggers and predispositions contributing to disease. In addition, we discuss the roles of other immune cells, including T cells and microglia, in the pathogenesis of AE. By analyzing therapeutic strategies and treatment responses we draw insights into AE pathophysiology. Written at a time of transformative therapeutic advancements through cell therapies this work underscores the synergy between detailed immunological research and the development of innovative therapies.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101955"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855085","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":"Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): Insights into pathogenesis and biomarkers of prognosis","authors":"Jane Andersen ,&nbsp;Fabienne Brilot","doi":"10.1016/j.smim.2025.101944","DOIUrl":"10.1016/j.smim.2025.101944","url":null,"abstract":"<div><div>MOG antibody-associated disease (MOGAD), an inflammatory demyelinating pathology, is typically associated with the clinical phenotypes acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), or transverse myelitis (TM). The mainstay of diagnosis is detection of antibodies targeting oligodendrocyte-expressed MOG (MOG-IgG). MOG-IgG-mediated demyelination occurs via complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), enhanced cognate T-cell CNS infiltration and activation, and oligodendrocyte cytoskeleton disruption, but the exact role of the immune system in MOGAD is still poorly understood. The disease course is either monophasic or relapsing, with relapsing course affecting approximately two-thirds of individuals. Neurological disability accumulates with relapse and may manifest as visual, motor, sensory, and cognitive deficits. Thus, accurate disease course prediction is of paramount importance. Prognostic biomarkers, implemented at a global scale, have the potential to guide timely therapeutic decisions to limit relapse-associated disability accrual while simultaneously avoiding unnecessary immunosuppression in monophasic individuals. This review explores recent insights in the understanding of MOGAD pathogenesis as well as advances in prognostic biomarkers of relapsing course and disease activity.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101944"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621427","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":"Interplay between the complement system and other immune pathways in the tumor microenvironment","authors":"Cecilia Garlanda ,&nbsp;Monica Dambra ,&nbsp;Elena Magrini","doi":"10.1016/j.smim.2025.101951","DOIUrl":"10.1016/j.smim.2025.101951","url":null,"abstract":"<div><div>Tumor growth and spread are sustained by the tumor microenvironment. Inflammatory cells and pathways have a fundamental role in the tumor microenvironment, driving or conditioning the functional activation of other leukocyte subsets and favoring evasion of anti-tumor immunity. One of the inflammatory pathways contributing to cancer-related inflammation is the complement system. Complement has long been considered an immune mechanism associated with immunosurveillance. More recently it emerged as a tumor promoting pathway, due to direct effects on cancer cells or indirect effects via immunosuppression driven by myeloid cells. The role of complement in cancer is complex and ambiguous, and depends on the tumor type and stage, as well as other factors including oncogenic drivers, leukocyte infiltration, interactions with other tumor microenvironment components or tumor cells. Other factors of complexity include the source of complement molecules, its canonical or non-canonical extracellular functions, its potential intracellular activation, and the interaction with other systems, such as the coagulation or the microbiome. Preclinical studies generally demonstrate the involvement of complement activation in smouldering inflammation in cancer and promotion of an immunosuppressive environment. These studies paved the way for clinical trials aimed at enhancing the potential of immunotherapy, in particular by targeting complement-dependent myeloid-sustained immunosuppression. However, the complex role of complement in cancer and the multiplicity of complement players may represent stumbling blocks and account for failures of clinical trials, and suggest that further studies are required to identify patient subsets who may benefit from specific complement molecule targeting in combination with conventional therapies or immunotherapy. Here, we will discuss the anti- or pro-tumor role of complement activation in cancer, focusing on the interactions of complement with immune cells within the tumor microenvironment, in particular the myeloid compartment. Furthermore, we will examine the potential of complement targeting in cancer treatment, particularly in the context of macrophage reprogramming.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101951"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individual- and population-associated heterogeneity in vaccine-induced immune responses. The impact of inflammatory status and diabetic comorbidity","authors":"Simone A. Joosten","doi":"10.1016/j.smim.2025.101964","DOIUrl":"10.1016/j.smim.2025.101964","url":null,"abstract":"<div><div>Vaccines induce quantitively and qualitatively different effector responses between populations but also between individuals within populations. Several factors are known to affect the success of vaccination, including age, gender, co-infections (e.g. HIV), pre-existing inflammatory status and co-morbidities such as type 2 diabetes mellitus (T2DM). These factors, either alone or in combination, strongly influence vaccine induced immunity and thereby possibly vaccine efficacy. Vaccination strategies should therefore not only be evaluated in young, healthy selected individuals but also in individuals with immune ageing, persisting inflammation and co-morbidities, and include the measurement of qualitative rather than only quantitative measures of vaccine effects.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101964"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923909","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":"Unraveling the pathophysiology of narcolepsy type 1 through hypothesis-driven and hypothesis-generating approaches","authors":"Sean A. Freeman ,&nbsp;Ikram Ayoub ,&nbsp;Yves Dauvilliers ,&nbsp;Roland S. Liblau","doi":"10.1016/j.smim.2025.101962","DOIUrl":"10.1016/j.smim.2025.101962","url":null,"abstract":"<div><div>Narcolepsy type 1 (NT1) is a chronic orphan neurological sleep disorder characterized by the loss of hypocretin-producing neurons in the lateral hypothalamus, which play a crucial role in wakefulness. Given the genetic association with the <em>HLA-DQB1 * 06:02</em> allele and environmental links with the 2009 influenza pandemic, many lines of evidence point towards an immune mechanism, notably autoimmunity, underlying the disease pathophysiology. Autoreactive T cells are found in the blood of NT1 patients, and mouse models demonstrate their migratory capacity and contribution in the selective destruction of hypocretin-producing neurons. However, direct evidence for their role in human NT1 pathophysiology remains elusive. In complementing these findings, hypothesis-generating approaches—including multiparametric immune profiling, transcriptomic sequencing and large-scale proteomic of blood and cerebrospinal fluid—have uncovered promising new avenues into the immune system’s involvement in NT1. In this review, we explore the mechanisms driving NT1 pathogenesis, emphasizing both hypothesis-driven and hypothesis-generating approaches, and discuss potential future directions that could pave the way for targeted immunotherapies.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101962"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948801","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":"The spatial and single-cell landscape of skin: Charting the multiscale regulation of skin immune function","authors":"Abiha Kazmi ,&nbsp;Raman Gill ,&nbsp;Paula Restrepo ,&nbsp;Andrew L. Ji","doi":"10.1016/j.smim.2025.101958","DOIUrl":"10.1016/j.smim.2025.101958","url":null,"abstract":"<div><div>Immune regulation is a key function of the skin, a barrier tissue that exhibits spatial compartmentalization of innate and adaptive immune cells. Recent advances in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have facilitated systems-based investigations into the molecular and cellular features of skin immunity at single-cell resolution, identifying cell types that maintain homeostasis in a coordinated manner, and those that exhibit dysfunctional cell-cell interactions in disease. Here, we review how technological innovation is uncovering the multiple scales of heterogeneity in the immune landscape of the skin. The microanatomic scale encompasses the skin’s diverse cellular components and multicellular spatial organization, which govern the functional cell interactions and behaviors necessary to protect the host. On the macroanatomic scale, understanding heterogeneity in cutaneous tissue architecture across anatomical sites promises to unearth additional functional immune variation and resulting disease consequences. We focus on how single-cell and spatial dissection of the immune system in experimental models and in humans has led to a deeper understanding of how each cell type in the skin contributes to overall immune function in a context-dependent manner. Finally, we highlight translational opportunities for adopting these technologies, and insights gleaned from them, into the clinic.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101958"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858985","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}