Immunological Reviews最新文献

{"title":"From Cell Death and Activation to Paralysis: Dysregulated Conventional Dendritic Cells in SIRS, Sepsis and Major Trauma Promote Immunosuppression","authors":"Mitra Ashayeripanah,&nbsp;Antoine Roquilly,&nbsp;Jose Villadangos","doi":"10.1111/imr.70087","DOIUrl":"10.1111/imr.70087","url":null,"abstract":"<div>\u0000 \u0000 <p>Conventional dendritic cells (cDC) are pivotal for initiating antigen-specific T-cell responses. Upon encountering pathogen- and damage-associated molecular patterns (PAMPs/DAMPs) or inflammation, cDC undergo <i>direct</i> or <i>indirect activation</i>. Directly activated cDC acquire additional antigens and present them to prime T-cells but become unresponsive to new antigens. In contrast, indirectly activated cDC remain capable of efficient antigen presentation upon subsequent exposure to PAMPs/DAMPs. Due to cDC's short lifespan, activated cDC are replenished within days by newly generated immature/resting cDC. However, during systemic inflammatory response syndrome (SIRS), early depletion and systemic activation of cDC can occur, followed by prolonged reprogramming that yields functionally impaired or <i>paralyzed/regulatory cDC.</i> These dysfunctional cDC populations contribute to post-SIRS immunosuppression. Gradual resolution of the immunoregulatory microenvironment allows repopulation with functionally competent cDC over subsequent weeks or months, necessary for restoring immunocompetence. In this review, we summarize current understanding of the sequential alterations in cDC population during SIRS, sepsis, and major trauma. We discuss the mechanistic basis of cDC dysfunction in these conditions as well as in tumors, highlighting shared and distinct pathways of dysregulation. We further elaborate on emerging therapeutic strategies aimed at restoring cDC function to improve immune recovery and clinical outcomes in critically ill patients.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"337 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950869","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":"Type 2 IgG Memory B Cells and Long-Lived IgE Plasma Cells in the Persistence of Allergy","authors":"Mariana C. G. Miranda-Waldetario,&nbsp;Weslley Fernandes-Braga,&nbsp;Maria A. Curotto de Lafaille","doi":"10.1111/imr.70089","DOIUrl":"10.1111/imr.70089","url":null,"abstract":"<div>\u0000 \u0000 <p>IgE antibodies mediate allergic reactions through their ability to bind to high affinity receptors on mast cells and basophils, triggering cell activation and degranulation upon crosslinking by allergens. The differentiation of IgE-producing cells is unique, as there is a paucity of IgE memory B cells and most IgE-expressing cells are plasma cells. High affinity IgE, however, is generated through sequential class switching from affinity-matured non-IgE memory B cells. Emerging studies have uncovered key features of the IgE response that are relevant to allergy development and persistence, including the existence of allergen-specific high affinity type 2 IgG memory cells that are poised to switch to IgE, and long-lived IgE plasma cells that reside in the bone marrow and secondary lymphoid organs. Here, we review how these processes sustain IgE memory and long-term allergic sensitization despite the short lifespan of circulating IgE.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"337 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931556","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":"Sex Differences in Asthma Pathogenesis","authors":"Kaitlin E. McKernan,&nbsp;Emely Henriquez Pilier,&nbsp;Dawn C. Newcomb","doi":"10.1111/imr.70100","DOIUrl":"10.1111/imr.70100","url":null,"abstract":"<p>There is a sex difference in asthma prevalence and asthma-related morbidity that changes from childhood into different reproductive stages of life. The impact of sex hormone signaling on asthma pathogenesis has been partially elucidated using large cohort human studies, human cells, and animal models. Androgens decreased airway inflammation by reducing type 2 inflammation and eosinophil infiltration as well as reducing neutrophil-induced airway inflammation in animal models. Estrogen signaling through ER-α increased IL-33 production, an alarmin produced by airway epithelial cells that increases type 2 inflammation and increased Th17 cell-mediated neutrophilic inflammation. Additional studies are needed to determine what happens to asthma control and asthma-induced inflammation in women during pregnancy and menopause as well as how sex differences in immune cell development and airway inflammation affect asthma incidence and onset during childhood. Collectively, understanding that sex differences in asthma risk and control exist throughout life is important to personalize therapies for males and females with asthma.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"337 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12783869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931482","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":"Hypertension as an Immune Disorder: From Cellular Drivers to Molecular Mediators","authors":"Kuniko Hunter,&nbsp;David G. Harrison","doi":"10.1111/imr.70093","DOIUrl":"10.1111/imr.70093","url":null,"abstract":"<div>\u0000 \u0000 <p>Hypertension is a major global health burden, affecting nearly half of the adult population and contributing significantly to morbidity and mortality. While traditionally viewed through its hemodynamic effects, growing evidence implicates immune dysregulation as a central driver of hypertension and its associated end-organ damage. Immune cells, including T cells, dendritic cells, and macrophages, infiltrate target organs and release mediators such as cytokines, reactive oxygen species, and metalloproteinases, promoting inflammation, fibrosis, and dysfunction. The discovery of isolevuglandin (IsoLG)-adducted neoantigens has advanced our understanding of antigen-dependent T cell activation in hypertension, revealing the roles of antigen-presenting cells, immune memory, and co-stimulatory pathways. Further, endothelial cells have emerged as non-professional antigen-presenting cells, orchestrating immune responses by modulating leukocyte recruitment and activation under mechanical and oxidative stress. Studies using experimental models and humans highlight the contributions of CD8⁺ T cells, immune memory formation, and altered sympathetic tone in perpetuating hypertension. Translational work has identified IsoLG-adducted peptides and their processing by the immunoproteasome as critical mechanisms driving immune activation. Collectively, these findings underscore the interplay between the immune system and hypertension, offering novel therapeutic opportunities to target immune-mediated mechanisms, mitigate blood pressure elevation, and reduce end-organ damage. This review highlights these advances while recognizing the growing body of literature in this evolving field.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"337 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905372","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":"Trained Immunity and Cardiovascular Risk: An Immunological Perspective","authors":"Katherine A. Boden,&nbsp;Jason Chai,&nbsp;Tafadzwa T. J. Kufazvinei,&nbsp;Robin P. Choudhury","doi":"10.1111/imr.70095","DOIUrl":"10.1111/imr.70095","url":null,"abstract":"<p>Systemic inflammation is a key driver of atherogenesis and its complications. While anti-inflammatory therapies targeting pathways such as IL-1β and IL-6 have shown promise in established atherosclerotic cardiovascular disease (ASCVD), potential systemic effects raise concerns about immune suppression and infection, underscoring the need for more precise immunomodulatory approaches. Trained immunity—a form of innate immune memory—has emerged as a potential contributor linking ASCVD risk factors to chronic inflammation and disease progression. In this review, we discuss the evidence for trained immunity in ASCVD, its induction by several known risk factors (e.g., hyperglycaemia, hypercholesterolemia, diet, chronic stress, inflammatory diseases, and infection), and its potential role in sustaining vascular inflammation. Advancing our understanding of the metabolic and epigenetic mechanisms underlying trained immunity, as well as defining shared and cumulative effects across risk factors, will be critical to guide the development of next-generation targeted therapies for ASCVD prevention and treatment.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"337 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12767646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898846","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":"Biology of IgE","authors":"Maria A. Curotto de Lafaille","doi":"10.1111/imr.70092","DOIUrl":"10.1111/imr.70092","url":null,"abstract":"&lt;p&gt;Almost 60 years ago, IgE antibodies were identified as a new immunoglobulin isotype responsible for hypersensitivity reactions to non-infectious substances [&lt;span&gt;1, 2&lt;/span&gt;]. Since then, there have been major advances in our understanding of how IgE functions in allergic diseases and in the immunological processes that drive the formation of IgE plasma cells. This volume on the Biology of IgE brings together expert reviews addressing the current state of knowledge on IgE cell development, the structural and cellular basis of IgE function, the role of IgE in allergic diseases, and genetic and early-life determinants of allergic sensitization.&lt;/p&gt;&lt;p&gt;High affinity IgE antibodies exert powerful biological effects, and their production is tightly regulated. IgE has the shortest half-life of all immunoglobulin isotypes, and the differentiation of IgE-producing cells involves several restrictive steps that limit the number of IgE plasma cells. Nevertheless, many allergies persist throughout life, implicating immunological memory maintained by allergen-specific memory B cells and IgE plasma cells. Miranda-Waldetario and collaborators (“Type 2 IgG memory B cells and long-lived IgE plasma cells in the persistence of allergy”) summarize current knowledge of the unique process that generates high affinity IgE and intrinsic features of IgE that contribute to pathogenicity [&lt;span&gt;3&lt;/span&gt;]. They also highlight the recent discovery of an IgG memory B-cell subset linked to allergic memory and the characterization of mature long-lived IgE plasma cells.&lt;/p&gt;&lt;p&gt;The main biological function of IgE antibodies derives from their ability to bind, in monomeric form, to the high affinity receptor FcεR1 on mast cells and basophils. Allergen-induced crosslinking of receptor-bound IgE triggers mast-cell activation and degranulation, initiating allergic reactions. IgE also binds to CD23 (FcεR2), expressed on naïve B cells and subsets of memory B cells. Charles and Blank (“IgE-Mediated Activation of Mast Cells and Basophils in Health and Disease”) review mast-cell and basophil biology and the IgE-mediated effector mechanisms that operate in both homeostatic and pathological contexts [&lt;span&gt;4&lt;/span&gt;]. Eggel and Jardetzky (“Structural and Functional Insights Into IgE Receptor Interactions and Disruptive Inhibition”) discuss structural features governing IgE-receptor binding and how therapeutic anti-IgE antibodies and emerging IgE-targeted approaches disrupt these interactions to block allergic reactions [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;IgE antibodies are extensively modified with N-linked glycans. Gyorgypal and collaborators (“Glycobiology of IgE”) analyze how IgE glycosylation influences receptor binding and IgE biological functions, including effects on serum clearance, interactions with FcεR1 and FcεR2, and downstream cellular responses [&lt;span&gt;6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Beyond their role in mast-cell and basophil activation, IgE antibodies can act as adjuvants by promoting antigen uptake b","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"337 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145891710","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":"AIRE's Complex Role Beyond Promiscuous Gene Expression","authors":"Pärt Peterson","doi":"10.1111/imr.70091","DOIUrl":"10.1111/imr.70091","url":null,"abstract":"<p>Central tolerance, established in the thymus, ensures T cells are nonreactive to self-antigens while maintaining a functional immune repertoire. Medullary thymic epithelial cells (mTECs) and thymic dendritic cells (DCs) play a crucial role in this mechanism by orchestrating the selection and deletion of autoreactive thymocytes, a process heavily influenced by the Autoimmune Regulator (AIRE). AIRE promotes the promiscuous expression of tissue-restricted antigens (TRAs) in mTECs, enabling the elimination of self-reactive T cells and the differentiation of regulatory T cells (Tregs). Studies on the role of AIRE in transcriptional regulation and nuclear body localization have significantly advanced our understanding of its mechanisms, revealing protein interactions with chromatin-associated complexes that facilitate broad transcriptomic complexity in mTECs. However, the discovery of neutralizing type 1 interferon (T1 IFN) autoantibodies in APECED patients, alongside recently identified AIRE-induced IFN signals in the thymus, suggests that AIRE's influence extends beyond its classical function in negative selection, potentially playing a broader role in thymic homeostasis via inflammatory signals. This review discusses recent advances in understanding AIRE's complexity, its role in transcriptional regulation and nuclear location, insights from studies in human APECED patients and rodent models, and the emerging concept of an IFN-mediated tonic inflammatory signal in the thymus.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"337 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12748037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145852885","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":"Dendritic Cells in the Gastrointestinal System: Division of Labor, Plasticity, and Niche-Specific Adaptation","authors":"Yixuan D. Zhou,&nbsp;Macy R. Komnick,&nbsp;Daria Esterházy","doi":"10.1111/imr.70090","DOIUrl":"10.1111/imr.70090","url":null,"abstract":"<p>The intestinal immune system is constantly challenged to distinguish between innocuous dietary antigens, commensal microbiota and intestinal self-antigens (self-Ags) versus harmful pathogens and malignant cells. It resides in the intestinal wall itself, Peyer's patches (PPs) and the draining lymph nodes (LNs). Dendritic cells (DCs) are found in all of these structures and are professional antigen-presenting cells (APCs) dictating and maintaining T cell fate. Here, we review how DCs contribute to immune homeostasis in the gastrointestinal system through multiple strategies: division in labor and strategic anatomical positioning between DC subtypes, plasticity and site-specific functional adaptation. While these properties of DCs are likely not unique to the gastrointestinal tract, it is the site where we have learned most about how this DC network operates.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"337 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12739599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825421","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":"T Peripheral Helper Cells in Lymphoid Aggregate and Tertiary Lymphoid Structure Formation","authors":"John Sowerby,&nbsp;Jaehyuk Choi,&nbsp;Deepak A. Rao","doi":"10.1111/imr.70088","DOIUrl":"10.1111/imr.70088","url":null,"abstract":"<div>\u0000 \u0000 <p>Lymphoid aggregates and more mature tertiary lymphoid structures frequently form within chronically inflamed tissues. These structures facilitate local T cell-B cell activation within an inflamed tissue, promoting the ongoing adaptive immune response. Target tissues in autoimmune diseases accumulate a range of CD4 T cells with the capacity to help B cells and promote lymphoid aggregate formation. These B cell-helper T cells include T peripheral helper (Tph) cells, which functionally resemble T follicular helper (Tfh) cells in their capacity to recruit and interact with B cells, yet differ primarily in their migratory capacity. Tph cells accumulate within inflamed tissues such as rheumatoid arthritis synovium, where they serve as a major source of the B cell chemoattractant CXCL13, which can drive recruitment of B cells to a peripheral tissue. Here, we discuss features of Tph cells and other Tfh-like T cell populations that accumulate within chronically inflamed tissues in autoimmune diseases and review the regulation of key factors produced by these cells, including CXCL13 and IL-21. Understanding the range of B cell-helper T cells that accumulate within tissues and the regulation of their differentiation and function may provide new strategies to either inhibit or promote their actions therapeutically.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"337 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802784","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":"Mechanosensing in Dendritic Cells","authors":"Vincent Calmettes,&nbsp;Melissa A. Quintanilla,&nbsp;Livia Lacerda Mariano,&nbsp;Matthieu Piel,&nbsp;Hélène D. Moreau,&nbsp;Ana-Maria Lennon-Duménil","doi":"10.1111/imr.70086","DOIUrl":"10.1111/imr.70086","url":null,"abstract":"<p>Since their discovery, dendritic cells have been recognized for their unusual capacity to sense and respond to physical stimuli within their environment. However, it took nearly two decades—and the advent of mechanobiology—to elucidate the underlying mechanisms and functional implications of this mechanical hypersensitivity. In this review, we first outline the fundamental principles by which cells interact with their physical surroundings and transduce mechanical cues into biological responses. We then examine these concepts in the context of dendritic cell biology, highlighting how mechanosensing shapes their immune phenotype and governs their migratory behavior across tissues. Emerging evidence reveals that dendritic cells possess remarkable adaptability to mechanical constraints, a property that critically defines their role in immune surveillance. These insights underscore the need to consider mechanical cues as key regulators of dendritic cell function, particularly in pathological settings where tissue mechanics are altered, such as cancer and fibrosis-associated autoimmune diseases.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"337 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754746","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}