Immunological Reviews最新文献_第2页

Complement Activation by Post-Translationally Modified Proteins: Links to Chronic Inflammation and Autoimmunity 翻译后修饰蛋白激活补体：与慢性炎症和自身免疫有关。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-09-16 DOI: 10.1111/imr.70166

Marleen M. J. van Greevenbroek, Leendert A. Trouw

{"title":"Complement Activation by Post-Translationally Modified Proteins: Links to Chronic Inflammation and Autoimmunity","authors":"Marleen M. J. van Greevenbroek, Leendert A. Trouw","doi":"10.1111/imr.70166","DOIUrl":"10.1111/imr.70166","url":null,"abstract":"<p>Post-translational modifications (PTMs) of proteins are essential to maintain homeostasis as many cellular processes rely on reversible PTMs. However, several PTMs, particularly irreversible PTMs in the extracellular space, can contribute to tissue dysfunction, inflammation, and may even trigger the development of autoimmunity against PTM-proteins. Such disease-associated PTMs are formed under conditions of metabolic stress, renal failure, smoking, or pollutants. Importantly, several of these PTMs have recently been shown to have the capacity to activate the complement system directly. These PTMs recruit C1q or Ficolin-3, thereby initiating complement activation. This induces on the one hand opsonins for clearance of (cellular) debris and on the other hand the production of inflammatory mediators. In many autoimmune diseases, patients develop a variety of autoantibodies against PTMs, further amplifying complement activation on PTM-proteins. Notably, anti-PTM antibodies are also present, albeit in lower concentrations, in diseases that are not characterized as typical autoimmune diseases. We therefore hypothesize that PTM-driven complement activation is an underlying factor for chronic low-level inflammation, thereby predisposing individuals to cardiovascular and metabolic diseases. In addition, the presence of complement activation fragments on PTM-proteins may facilitate the breakdown of immune tolerance towards PTM-proteins, further facilitating the production of anti-PTM autoantibodies. Finally, several interventions are discussed that either decrease the PTM-proteins or provide targeted complement inhibition specifically on PTM-proteins. Altogether, complement activation by PTM-proteins may represent an underestimated contributor to chronic inflammation.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975311","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}

引用次数: 0

Human Peripheral B Cell Subsets 人类外周B细胞亚群：关于B细胞生物学的进化概念和B细胞在疾病中的广泛相关性。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-09-14 DOI: 10.1111/imr.70177

Shiv Pillai, Elif Çakan, Anson Hui

引用次数: 0

Autoantibodies and T Cells Target Citrullinated and Homocitrullinated Antigens in Rheumatoid Arthritis 类风湿性关节炎的自身抗体和T细胞靶向瓜氨酸化和高瓜氨酸化抗原。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-09-14 DOI: 10.1111/imr.70178

Eddie A. James, Aisha Callebaut, Jane H. Buckner, William W. Kwok

{"title":"Autoantibodies and T Cells Target Citrullinated and Homocitrullinated Antigens in Rheumatoid Arthritis","authors":"Eddie A. James, Aisha Callebaut, Jane H. Buckner, William W. Kwok","doi":"10.1111/imr.70178","DOIUrl":"10.1111/imr.70178","url":null,"abstract":"<div>\u0000 \u0000 <p>Rheumatoid Arthritis (RA) is a prevalent form of inflammatory arthritis in which post-translational modifications are known to play a major role in the loss of tolerance. This review summarizes current knowledge of the role that such modifications play in the disease. Most individuals with RA have antibody responses directed against citrullinated and/or carbamylated self-antigens, but additional modifications are under active investigation. Post-translational modifications can alter the primary protein sequence, increasing binding to HLA molecules and recognition by T cells, and can generate new epitopes that are recognized by autoantibodies. They can also perturb protein structure and alter protein processing, enhancing presentation of cryptic epitopes. Finally, these modifications can alter protein function, potentially undermining cellular identity and function. Potentiation of post-translational modifications has been directly linked to environmental exposures that are epidemiologically tied to RA risk. The immunogenic effects of protein modification are associated with key variants that confer genetic risk for RA. Notably, immune assays designed to measure antibody recognition and monitor T cell responses directed against citrullinated and carbamylated antigens have emerged as useful biomarkers of disease risk and activity. The pathways of protein citrullination and carbamylation are also important targets for potential preventative and curative therapies.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965802","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}

引用次数: 0

Defining Functional T Cell Receptor Repertoires With Nanovial-Based Screening 用纳米微球筛选确定功能性T细胞受体谱。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-09-09 DOI: 10.1111/imr.70171

Dino Di Carlo

{"title":"Defining Functional T Cell Receptor Repertoires With Nanovial-Based Screening","authors":"Dino Di Carlo","doi":"10.1111/imr.70171","DOIUrl":"10.1111/imr.70171","url":null,"abstract":"<div>\u0000 \u0000 <p>T-cell receptor repertoires are commonly characterized through sequence diversity and antigen binding, while the cellular functions associated with individual receptors are often measured separately. In this review, I consider how functional information can be incorporated more directly into repertoire analysis by linking receptor identity with measurable effector outputs at single-cell resolution. I focus on Nanovial-based technologies that combine antigen-specific capture, stimulation, secretion measurement, viable-cell recovery, and downstream sequencing in workflows compatible with flow cytometry and single-cell sequencing platforms. Studies using conventional peptide–major histocompatibility complex ligands, the non-classical antigen-presenting molecules MR1 and CD1d, and secretion-encoded single-cell sequencing illustrate how these approaches can complement binding-based enrichment by adding information about secretory effector responses. I also discuss the extension of this framework from ligand-defined screening to dyad-resolved assays involving target cells, which can reveal how receptor identity relates to transcriptional and functional programs arising during direct cell–cell interactions. Together, these developments provide tools for studying relationships among TCR sequence, antigen recognition, and cellular response, with potential applications in therapeutic receptor discovery and in generating datasets for predictive models of T-cell function.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917784","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}

引用次数: 0

T Cell Thoughts T细胞的想法。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-09-08 DOI: 10.1111/imr.70172

Dmitry M. Chudakov

{"title":"T Cell Thoughts","authors":"Dmitry M. Chudakov","doi":"10.1111/imr.70172","DOIUrl":"10.1111/imr.70172","url":null,"abstract":"<div>\u0000 \u0000 <p>This review does not aspire to provide comprehensive coverage of any particular area. Rather, it is an attempt to reconsider and summarize the results produced by our team in the field of TCR repertoires over the past 15 years, and to correct some of the errors along the way. As intended, it is unavoidably subjective, one-sided, and full of citations to the author's publications. Nevertheless, I hope it will be useful to the immunological community. Someone, having read this relatively short text, will realize that there is no need to spend time studying our previous publications. And one might discover the only useful point of our collective effort hidden in a Supplementary Figure X of a previously unnoticed publication Y. The key points are formulated below as a set of short chapters. Their order does not follow the chronology of the cited works and only intermittently resembles a coherent narrative. In an attempt to summarize, we will speak here about the TCR repertoire preferences of T cell subsets, the plasticity and stubbornness of clonal memory, the price we pay for the privilege of possessing adaptive immunity, some secrets of healthy longevity, about repertoire-based diagnostics, and about immunotherapeutic approaches considered as a toolbox for correcting mistakes made by the immune system.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910172","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}

引用次数: 0

What Antibody Repertoires See: Structural and Immunogenetic Insights Into Influenza A Virus Hemagglutinin Recognition 抗体谱所见：甲型流感病毒血凝素识别的结构和免疫遗传学见解。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-09-08 DOI: 10.1111/imr.70176

Bruno Bonnettaz, Goran Bajic

{"title":"What Antibody Repertoires See: Structural and Immunogenetic Insights Into Influenza A Virus Hemagglutinin Recognition","authors":"Bruno Bonnettaz, Goran Bajic","doi":"10.1111/imr.70176","DOIUrl":"10.1111/imr.70176","url":null,"abstract":"<p>Human infection with or vaccination against influenza A virus has been one of the most informative systems for understanding how human antibody repertoires recognize viral glycoproteins. Decades of antibody isolation, repertoire sequencing, lineage tracing, serology, viral antigenic evolution, and structural biology have shown that antibody recognition is not simply a matter of “which epitope is targeted.” Instead, each surface on the viral hemagglutinin (HA) presents a distinct structural problem for the immune system. Repeated exposures through infection and vaccination coupled with continuous antigenic drift generate complex immune histories and reveal which viral surfaces evolve under antibody pressure. Structural studies have transformed the field by showing how antibody repertoires solve epitope-specific recognition problems. Some epitopes, such as the HA central stem, recruit highly stereotyped genetic and structural solutions. Others, such as the receptor-binding site, can be approached by genetically diverse antibodies that converge on common structural solutions of receptor mimicry. Additional epitopes, including the lateral patch, anchor, head interface, and head-stem junction, reveal intermediate patterns of repertoire constraint. Together, these examples show that what antibody repertoires “see” is determined by the interplay between viral glycoprotein structure, B cell precursor availability, somatic evolution, and population-level immunoglobulin diversity.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910161","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}

引用次数: 0

Activation of Anergic B Cells During Development of Autoimmunity 自身免疫发展过程中无能B细胞的活化。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-09-06 DOI: 10.1111/imr.70175

Mohammad Mansoor, Brandon K. Hilliard, Mia J. Smith

{"title":"Activation of Anergic B Cells During Development of Autoimmunity","authors":"Mohammad Mansoor, Brandon K. Hilliard, Mia J. Smith","doi":"10.1111/imr.70175","DOIUrl":"10.1111/imr.70175","url":null,"abstract":"<p>In healthy individuals, autoreactive B cells are normally silenced via central and peripheral tolerance mechanisms. In the periphery, when autoreactive B cells recognize self-antigen via their B cell receptor (BCR) (signal 1) but do not receive T cell help (signal 2), they undergo the tolerance mechanism called anergy. Human anergic B cells are termed B<sub>ND</sub> (Naïve IgD+ B cells). Previous studies have shown that B<sub>ND</sub> cells are decreased in the peripheral blood of individuals with autoimmunity, suggesting they may have become activated and contributed to the development of disease. In line with this, recently it has been found that a portion of the remaining anergic B cells present in the blood of autoimmune individuals exhibit an activated phenotype. In this review, we will summarize what is known and unknown about these cells, including their relation to other recognized autoreactive B cell subsets, how they become activated in the first place, and what their pathogenic functions are. Understanding how B<sub>ND</sub> cells break tolerance and contribute to disease will advance the development of new therapeutic approaches and highlight novel cell populations amenable to depletion.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899845","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}

引用次数: 0

Structural T-Cell Receptor Analysis in the Age of Machine Learning 机器学习时代的结构t细胞受体分析。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-09-05 DOI: 10.1111/imr.70168

Nele P. Quast, Matthew I. J. Raybould, Charlotte M. Deane

引用次数: 0

Plasma Cell Selection and Migration in the Establishment of Long-Lived Antibody Responses 长期抗体反应建立中的浆细胞选择和迁移。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-09-05 DOI: 10.1111/imr.70173

Wataru Ise, Kazuhiro Suzuki, Tomohiro Kurosaki

引用次数: 0

Mapping the Altered Landscape of TCR Repertoire in Autoimmune Diseases 自身免疫性疾病中TCR库的改变

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-09-04 DOI: 10.1111/imr.70174

Celine Albalaa, Martin Pezous, David Klatzmann, Encarnita Mariotti-Ferrandiz

{"title":"Mapping the Altered Landscape of TCR Repertoire in Autoimmune Diseases","authors":"Celine Albalaa, Martin Pezous, David Klatzmann, Encarnita Mariotti-Ferrandiz","doi":"10.1111/imr.70174","DOIUrl":"10.1111/imr.70174","url":null,"abstract":"<p>Autoimmune diseases arise from the breakdown of immune tolerance through complex interactions between genetic predisposition, environmental exposures, and adaptive immune responses. High-throughput T-cell receptor (TCR) repertoire sequencing has transformed our ability to characterize these responses, providing unprecedented insights into clonal dynamics, antigen-driven selection, and immune history. In this review, we summarize the major alterations of TCR repertoires reported across autoimmune diseases, including changes in diversity, clonal expansion, repertoire architecture, and tissue distribution. We discuss the principal biological and technical challenges that currently limit repertoire interpretation, with particular emphasis on the concept that bulk repertoires represent composite mixtures of biologically distinct T-cell populations. Finally, we highlight emerging approaches integrating single-cell profiling, computational modeling, and antigen-specificity inference that are reshaping the field. We propose that TCR repertoires should be viewed as dynamic molecular footprints of autoimmune disease, providing a systems-level framework to improve mechanistic understanding, biomarker discovery, and the development of precision immunotherapies.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890507","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}

引用次数: 0