Seminars in Immunology最新文献

{"title":"The glycoimmune landscape in health and disease","authors":"Salomé S. Pinho ,&nbsp;Gabriel A. Rabinovich","doi":"10.1016/j.smim.2025.101965","DOIUrl":"10.1016/j.smim.2025.101965","url":null,"abstract":"<div><div>Emerging observations at the molecular, cellular, and organismal levels have unveiled critical roles for glycans in regulating a broad range of innate and adaptive immune cell processes. Through interactions with various families of glycan-binding proteins, including galectins, C-type lectins, and siglecs, glycans shape the nature, the fate and the function of immune cell types, modulating processes such as immune cell development, activation, differentiation, trafficking, exhaustion, and survival. Furthermore, dysregulated glycosylation pathways and altered glycan-binding receptor functions are associated with several pathological conditions, including infection, autoimmunity, and cancer. This special issue highlights the most recent updates and current challenges on the multifunctional roles of glycans and glycan-binding proteins in orchestrating, amplifying, or inhibiting immune responses. This collection seeks to enhance awareness of the significance of glycans in immunobiology and immunopathology from cellular, molecular, and evolutionary perspectives into clinical applications, underscoring their relevance as promising biomarkers and targets for designing novel immunotherapeutic approaches.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101965"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098465","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":"Differential immune responses behind different celiac disease manifestations","authors":"Esko Kemppainen,&nbsp;Olga Albó,&nbsp;Helka Kaunisto,&nbsp;Emilia Siukola,&nbsp;Katri Lindfors","doi":"10.1016/j.smim.2025.101941","DOIUrl":"10.1016/j.smim.2025.101941","url":null,"abstract":"<div><div>In celiac disease (CeD), dietary gluten serves as the driver for a comparatively well characterized small bowel mucosal immune response that generally results in small bowel mucosal villous atrophy and crypt hyperplasia along with a disease-specific transglutaminase 2 (TG2) targeting autoantibody response. Individuals with positive TG2 autoantibodies but normal small intestinal mucosal morphology are regarded at increased risk of developing CeD and represent patients with potential CeD. The removal of gluten from the diet leads to disappearance of the autoantibodies and normalization of the mucosal architecture in most cases. However, refractory CeD patients deviate from this dogma as they present with abnormal T cell compartment, persistent symptoms and villous atrophy despite a strict gluten-free diet. The heterogeneity of CeD presentation is further diversified by varying symptomatology. Gastrointestinal symptoms are the most canonical signs of CeD, and they include for instance diarrhea, vomiting, constipation and abdominal pain. Yet, a great portion of the patients manifest the disease at extraintestinal sites such as skin, musculoskeletal system or neuronal tissues. Beyond the involvement of various transglutaminase autoantibodies, the detailed immune mechanisms contributing to the development of these manifestations remains elusive, though. This review highlights the current understanding of the immunological differences in various manifestations of CeD. As the immunological basis of the different CeD phenotypes is at present insufficiently understood, more research on the subject is warranted before such data could be maximally applied to clinical practice.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101941"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621426","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":"Cellular stress and macrophage activation","authors":"Jing Yu,&nbsp;Bin-Zhi Qian","doi":"10.1016/j.smim.2025.101953","DOIUrl":"10.1016/j.smim.2025.101953","url":null,"abstract":"<div><div>Cellular stress responses are pivotal in maintaining tissue homeostasis and intricately linked with various diseases. Macrophages, a key player of innate immune system, exhibit remarkable plasticity and responsiveness to environmental cues. In response to various cellular stresses, macrophages contribute to tissue homeostasis and disease progression via specialized activation/polarization associated with distinctive phenotypes and functions. This review provides an overview of the intricate interplay between cellular stress responses and macrophage activation, summarizing recent advancements and offering insights into potential therapeutic strategies.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143820677","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":"Global aspects of celiac disease and food allergy","authors":"Samagra Agrawal,&nbsp;Govind K. Makharia","doi":"10.1016/j.smim.2025.101961","DOIUrl":"10.1016/j.smim.2025.101961","url":null,"abstract":"<div><div>Celiac disease and food-allergy are both food-related chronic immune disorders with a common pathogenic link being breakdown in the gut tolerance to otherwise innocuous food antigens. Notwithstanding the similarities, there are significant differences in the pathogenesis of both disorders, which translates to variations in clinical presentations, diagnostic tools and disease epidemiology. The past few decades have witnessed a global increase in prevalence and incidence of both disorders, driven both by true rise due to epidemiological factors and unmasking of previously undiagnosed disease due to better diagnostics and health seeking behavior, related to economic factors. Worldwide as more cases are diagnosed, disparities in healthcare and resources available for disease management are increasingly becoming more relevant but are infrequently discussed. In this review we will discuss the global epidemiology of celiac disease and food allergy, their epidemiological risk factors and future directions for their improved diagnosis and management.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101961"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879308","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":"Variable domain glycosylation as a marker and modulator of immune responses: Insights into autoimmunity and B-cell malignancies","authors":"Roxane Biersteker ,&nbsp;Oliver F. Larsen ,&nbsp;Manfred Wuhrer ,&nbsp;Tom W.J. Huizinga ,&nbsp;René E.M. Toes ,&nbsp;Lise Hafkenscheid","doi":"10.1016/j.smim.2025.101946","DOIUrl":"10.1016/j.smim.2025.101946","url":null,"abstract":"<div><div>Glycosylation of antibodies is essential for shaping immune responses, as it contributes significantly to antibody function and diversity. While immunoglobulin G (IgG) Fc glycosylation is well-characterized, variable domain glycosylation (VDG) introduces an additional and less understood layer of complexity. Notably, VDG is associated with rheumatoid arthritis, where disease-specific IgG autoantibodies abundantly express this modification. Moreover, its presence on these antibodies correlates with disease progression in at-risk individuals and therapeutic outcomes. Emerging evidence links increased VDG levels to other autoimmune diseases and B-cell malignancies, highlighting its potential as both a marker and modulator in disease onset and progression. Importantly, VDG on IgG is now recognized to influence antigen binding, enhance antibody stability, and modulate interactions with the human neonatal Fc receptor. In addition, glycans in the antigen-binding domains of autoreactive B-cell receptors (BCRs) can significantly impact B cell activation. In follicular lymphoma and other B-cell malignancies, the presence of <em>N-</em>glycosylation sites in the immunoglobulin variable domains leads to the introduction of oligomannose glycans, which are postulated to bind to mannose-specific lectins. This interaction might promote antigen-independent activation of BCRs, thereby supporting malignant B cell survival and proliferation. Here, we explore the regulatory pathways of VDG and its functional roles across both physiological and pathological conditions, underscoring its prevalence and significance in various autoimmune diseases and B-cell malignancies. Ultimately, advancing our understanding of the regulatory factors influencing VDG and its functional implications could be highly rewarding for identifying potential therapeutic targets and strategies to prevent and treat autoimmune diseases and B-cell malignancies.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101946"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724882","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 therapies in coeliac disease and food allergies: Advances, challenges, and opportunities","authors":"Dianne E. Campbell ,&nbsp;Sam Mehr ,&nbsp;Olivia G. Moscatelli ,&nbsp;Robert P. Anderson ,&nbsp;Jason A. Tye-Din","doi":"10.1016/j.smim.2025.101960","DOIUrl":"10.1016/j.smim.2025.101960","url":null,"abstract":"<div><div>Coeliac disease and food allergy management primarily relies on the strict avoidance of dietary antigens. This approach is challenging to maintain in real-world settings and in food allergy carries the risk of life-threatening anaphylaxis. Despite their distinct pathogenesis, both disorders are driven by maladaptive responses to dietary proteins, creating opportunities for shared treatment strategies. In food allergy, desensitisation therapies such as oral, sublingual, and epicutaneous immunotherapy are well-established, complemented by biologics like omalizumab and dupilumab. However, the induction of sustained tolerance remains challenging. In contrast, therapeutic advancements for coeliac disease are still in their early stages. Current efforts focus on gluten detoxification or modification, immune blockade or modulation, tolerogenic approaches, and barrier restoration. Emerging therapies, including JAK and BTK inhibitors and microbiome-targeted interventions, support further targeted treatment options for both conditions. Biomarkers tracking gluten-specific T cells have emerged as valuable tools for immunomonitoring and symptom assessment in coeliac disease, although standardisation of patient-reported outcome measures and gluten challenge protocols is still needed. Food allergy trials are reliant on double-blind placebo-controlled food challenges to measure allergen reactivity, but these are time-consuming, carry risks, and underscore the need for surrogate biomarkers. The successful development of immune-targeted therapies will require building an immune toolset to optimally assess systemic responses to antigens in both conditions. Clinically, this could lead to better outcomes for patients who might otherwise remain undiagnosed or untreated due to the absence of significant enteropathy or allergen-specific symptoms.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101960"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864235","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":"Acetylation and deacetylation dynamics in stress response to cancer and infections","authors":"Lili Li ,&nbsp;Yanqiong Zeng ,&nbsp;Genhong Cheng ,&nbsp;Heng Yang","doi":"10.1016/j.smim.2025.101957","DOIUrl":"10.1016/j.smim.2025.101957","url":null,"abstract":"<div><div>In response to stress stimuli, cells have evolved various mechanisms to integrate internal and external signals to achieve dynamic homeostasis. Lysine acetyltransferase (KATs) and deacetyltransferase (KDACs) are the key modulators of epigenetic modifications, enabling cells to modulate cellular responses through the acetylation and deacetylation of both histone and nonhistone proteins. Understanding the signaling pathways involved in cellular stress response, along with the roles of KATs and KDACs may pave the way for the development of novel therapeutic strategies. This review discusses the molecular mechanisms of acetylation and deacetylation in stress responses related to tumorigenesis, viral and bacterial infections. In tumorigenesis section, we focused on the tumor cells’ intrinsic and external molecules and signaling pathways regulated by acetylation and deacetylation modification. In viral and bacterial infections, we summarized the update research on acetylation and deacetylation modification in viral and bacterial infections, which systematical introduction on this topic is not too much. Additionally, we provide an overview of current therapeutic interventions and clinical trials involving KAT and KDAC inhibitors in the treatment of cancer, as well as viral and bacterial infection-related diseases.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101957"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877360","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":"Neuroimmune interactions between itch neurons and skin microbes","authors":"Sharan Kumar Balaji ,&nbsp;Waris Muhammad Khuwaja ,&nbsp;Md Liakat Hossain ,&nbsp;Luchiano Giovanni Benjamin Fernando,&nbsp;Xintong Dong","doi":"10.1016/j.smim.2025.101933","DOIUrl":"10.1016/j.smim.2025.101933","url":null,"abstract":"<div><div>Itch is an unpleasant sensation that is encoded by specific sensory neurons called pruriceptors. Itch is associated with almost all skin diseases. Recent studies revealed that many itchy skin diseases are associated with microbiome dysbiosis. Pathogenic microbes secrete proteases and toxins to invade skin cells. Some microbial products can directly activate sensory neurons, while others activate the mammalian immune system and indirectly cause itch. In this review, we summarize the current knowledge on microbe-immune-neuron crosstalks and discuss their relevance in itchy skin diseases.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101933"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580292","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":"Endogenous glucocorticoids and human immunity: Time to revisit old dogmas","authors":"Brinda Bhatt ,&nbsp;Luis M. Franco","doi":"10.1016/j.smim.2025.101949","DOIUrl":"10.1016/j.smim.2025.101949","url":null,"abstract":"<div><div>Glucocorticoids (GCs) are steroid hormones with diverse and important roles in the physiologic response to stress. These include permissive and suppressive effects on immunity, which help prepare the organism for future infectious stressors and control the immunological response to a recent stressor, preventing autoimmune damage. The ability of GCs to rapidly suppress an overactive immune system has been harnessed pharmacologically and synthetic GCs have played a central role in the treatment of inflammatory and autoimmune diseases for the past eight decades. Given their importance in clinical medicine, an emphasis on the anti-inflammatory and immunosuppressive effects of synthetic GCs has overshadowed the study of the physiologic roles of endogenous GCs in human immunity. The rising interest in the intersection between neurobiology and immunity, and the development of technologies that facilitate direct experimentation with human cells and tissues, make this an ideal time to critically review existing knowledge on this subject. In this review of the past 100 years of biomedical literature on the effects of endogenous glucocorticoids on human immunity, we summarize existing experimental evidence, reveal key knowledge gaps and misconceptions, and highlight specific areas of opportunity for new research.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101949"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791907","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":"Interferon regulatory factor 3 beyond innate immunity: Regulation in obesity and metabolic disorders","authors":"Heng Li ,&nbsp;Yongliang Zhang ,&nbsp;Hong Yong Peh","doi":"10.1016/j.smim.2025.101948","DOIUrl":"10.1016/j.smim.2025.101948","url":null,"abstract":"<div><div>Interferon regulatory factor 3 (IRF3) is a transcription factor known primarily for its role in antiviral immunity via regulation of type I interferons (IFNs). Recent research has broadened its significance to encompass metabolic disorders, particularly obesity and diabetes. Obesity is characterized by chronic low-grade inflammation, insulin resistance, and metabolic dysfunction, all of which are increasingly found to be associated with immune signaling pathways. IRF3 has emerged as an important regulator in the development of obesity and type 2 diabetes (T2D), predominantly through its regulation of inflammatory cytokines production in various cells in adipose tissue. In obese individuals, IRF3 is activated in the adipocytes and adipose tissue macrophages, to promote the expression of inflammatory cytokines, thereby contributing to chronic inflammation and exacerbating insulin resistance. Moreover, IRF3 has been linked to mitochondrial dysfunction in hepatic disorders, further amplifying metabolic stress and imbalances associated with obesity. The growing evidence suggests that IRF3 is an important mediator in both immune and metabolic pathways, highlighting its potential as a target for the development of therapeutic interventions for obesity-related inflammation and metabolic dysfunction.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"78 ","pages":"Article 101948"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715135","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}