Immunological Reviews最新文献_第4页

From Disposal to Display: Crinophagy as a β-Cell Source of Neoantigens in Type 1 Diabetes 从处置到展示：噬细胞作为1型糖尿病新抗原的β细胞来源。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-08-03 DOI: 10.1111/imr.70156

Angela J. Zou, Xiaoxiao Wan

{"title":"From Disposal to Display: Crinophagy as a β-Cell Source of Neoantigens in Type 1 Diabetes","authors":"Angela J. Zou, Xiaoxiao Wan","doi":"10.1111/imr.70156","DOIUrl":"10.1111/imr.70156","url":null,"abstract":"<div>\u0000 \u0000 Type 1 diabetes (T1D) arises when autoreactive lymphocytes target pancreatic β-cells, yet the mechanisms that convert β-cell self-proteins into disease-relevant antigens remain incompletely defined. β-cells are uniquely positioned to generate neoantigens because they devote extraordinary protein synthesis capacity to insulin production and maintain thousands of dense-core insulin granules. While a small fraction of granules undergoes glucose-stimulated exocytosis, excess, aged, or immature granules can be degraded through crinophagy, a lysosomal pathway in which secretory granules fuse with lysosomes to form crinosomes. Recent immunopeptidomic studies suggest that crinosomes are not merely disposal compartments but antigen-editing organelles that remodel insulin granule cargo into pathogenic epitopes. These include free insulin B-chain peptides, hybrid insulin peptides, post-translationally modified insulin and C-peptide epitopes, and stress-induced insulin sequence variants such as insulin B-peptide C19S. Because several crinosome-associated epitopes are poorly represented in the thymus, crinophagy may create a peripheral antigen repertoire that permits escape from central tolerance and activation of autoreactive T cells in islets and draining lymphoid tissues. This review discusses the physiology of β-cell granule turnover, the mechanisms of crinosome-associated neoantigen generation, and their implications for T1D pathogenesis, biomarkers, and therapeutic targeting.\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"341 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667825","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

B1 Cells for Life. B1生命细胞。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-08-01 DOI: 10.1111/imr.70160

Thomas L Rothstein

引用次数: 0

The Influenza-Specific Immunoglobulin Repertoire - Nimble Yet Steeped in Tradition. 流感特异性免疫球蛋白的剧目-灵活，但浸透在传统。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-08-01 DOI: 10.1111/imr.70164

Sarah F Andrews, Masaru Kanekiyo

{"title":"The Influenza-Specific Immunoglobulin Repertoire - Nimble Yet Steeped in Tradition.","authors":"Sarah F Andrews, Masaru Kanekiyo","doi":"10.1111/imr.70164","DOIUrl":"10.1111/imr.70164","url":null,"abstract":"Influenza virus has circulated in the human population and co-evolved with us for centuries or longer, shaping our immune repertoires through a continuous host-virus arms race. Across individuals, antibodies repeatedly converge on shared solutions for capturing this shape-shifting virus by precisely targeting conserved sites of vulnerability-sites the virus cannot alter without functional cost-through structural features encoded directly by germline immunoglobulin genes. These recurring public antibodies, termed multi-donor class antibodies, have been pivotal for understanding human anti-influenza immunity and in guiding vaccine strategies that may shift the balance of the host-virus arms race. As single-cell biology, structural biology, and computational approaches mature, previously uncharted areas of our immune repertoires are coming into view. Here, we review the current understanding of the influenza-specific immune repertoire, focusing on antibodies and multi-donor antibody classes directed toward antigenic supersites on viral hemagglutinin and neuraminidase-the two major targets of protective antibodies-and discuss how these insights may advance the development of game-changing influenza vaccines.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"341 1","pages":"e70164"},"PeriodicalIF":10.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816742","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

The Developmental and Functional Implications of Age-Associated B Cells (ABCs) Across Tissue Microenvironments. 年龄相关B细胞（abc）在组织微环境中的发育和功能意义。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-08-01 DOI: 10.1111/imr.70162

Rebecca L Francis, Jason S Weinstein

{"title":"The Developmental and Functional Implications of Age-Associated B Cells (ABCs) Across Tissue Microenvironments.","authors":"Rebecca L Francis, Jason S Weinstein","doi":"10.1111/imr.70162","DOIUrl":"10.1111/imr.70162","url":null,"abstract":"Age-associated B cells (ABCs) are a dynamic B cell subset whose identity, development, and function are fundamentally shaped by the tissue microenvironments in which they reside. Primarily defined by expression of CD11c and T-bet, ABCs arise across diverse contexts, including aging, infection, autoimmunity, and cancer, yet exhibit striking heterogeneity that reflects the distinct signals present in each tissue niche. While the core generative cues of TLR7/9 activation, IFN-γ, IL-21, and BCR stimulation are common, the local tissue environment dictates how these signals are integrated and which functional properties are ultimately expressed. In infectious environments, altered splenic structure, peripheral tissue inflammation, and organ-specific cytokine gradients influence context-dependent ABC phenotypes with unique localization and effector characteristics. In autoimmune diseases, target organ microenvironments provide the TLR ligands, cytokines, and cellular interactions that sustain local ABC expansion and pathogenic activity. Similarly, in the tumor microenvironment, ABCs are shaped by tertiary lymphoid structures and chronic inflammatory signals that can shift their function between pro-inflammatory and immunosuppressive states. This review explores how tissue microenvironments influence ABC biology in infections, autoimmunity, and cancer, highlighting critical implications for understanding disease mechanisms and developing targeted therapeutic strategies.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"341 1","pages":"e70162"},"PeriodicalIF":10.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811528","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

Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity 超越序列：自身免疫中抗原的翻译后重构

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-07-30 DOI: 10.1111/imr.70150

Cynthiya Shrestha, Holly M. Weisfelder, Thanh D. Do

{"title":"Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity","authors":"Cynthiya Shrestha, Holly M. Weisfelder, Thanh D. Do","doi":"10.1111/imr.70150","DOIUrl":"https://doi.org/10.1111/imr.70150","url":null,"abstract":"Autoimmune responses are often attributed to failed tolerance to self-proteins, yet protein expression alone cannot explain why certain antigens dominate disease, why autoreactivity emerges under stress, or why specific HLA alleles shape risk. This review presents a framework in which autoimmunity arises from posttranslational remodeling of antigen identity. Rather than limiting PTMs to side chain chemistry, we consider how covalent modifications, altered processing, aberrant translation, peptide recombination, and supramolecular assembly expand the repertoire of molecular forms available for immune recognition. Classical PTMs such as citrullination, deamidation, oxidation, glycosylation, phosphorylation, sulfation, and ubiquitin-like remnants can modify proteolysis, HLA binding, and antibody recognition. Noncanonical pathways, including signal peptide processing, ERAP-dependent trimming, defective ribosomal products, cryptic ORFs, proteasome-catalyzed splicing, and hybrid insulin peptides, further demonstrate that the presented antigenome extends beyond annotated proteins. We also propose that aggregation functions as a supramolecular antigenic modification by altering uptake, persistence, protease accessibility, and local reaction chemistry. Examples from rheumatoid arthritis, celiac disease, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, and autoimmune thyroid disease illustrate how these mechanisms converge. Finally, we discuss mass spectrometry and immunopeptidomics strategies for identifying, validating, and functionally interpreting remodeled antigens in autoimmune disease.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"341 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616898","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

Targeting Inflammation in Atherosclerotic Cardiovascular Disease: Mechanisms and Emerging Therapies 动脉粥样硬化性心血管疾病的靶向炎症：机制和新兴疗法

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-07-29 DOI: 10.1111/imr.70151

M. P. Spindler, P. Libby, P. M. Ridker

{"title":"Targeting Inflammation in Atherosclerotic Cardiovascular Disease: Mechanisms and Emerging Therapies","authors":"M. P. Spindler, P. Libby, P. M. Ridker","doi":"10.1111/imr.70151","DOIUrl":"https://doi.org/10.1111/imr.70151","url":null,"abstract":"<div>\u0000 \u0000 A large body of evidence has helped reframe atherosclerotic cardiovascular disease from a mere lipid storage disorder to a chronic inflammatory disease. Both innate and adaptive immune pathways contribute to atherogenesis, plaque progression, and plaque destabilization. Macrophages, T cells, and cytokines—among them IL-1β, IL-6, and IL-18—have emerged as key immune cells and mediators implicated in atherosclerosis progression. Residual inflammatory risk—as measured by highly sensitive C-reactive protein (hsCRP) – has gained broad clinical acceptance as an important biomarker of cardiovascular risk prediction independent of cholesterol burden. Finding strategies that target residual inflammatory risk has proven an elusive goal in preventative cardiology. Specific approaches—such as IL-1β inhibition or low-dose colchicine—have shown benefit in reducing cardiovascular events, while other strategies have failed, underscoring the importance of targeting disease-relevant immune pathways and selecting patients that will benefit. Newer approaches—including IL-6 inhibitors, NLRP3 inflammasome inhibitors, and low-dose IL-2—offer promise for further risk reduction. Efforts to use inflammatory biomarkers to more precisely identify patients who may benefit may further improve the benefit-to-risk profile of emerging therapies.\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"341 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616396","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

GC B Cells, Tfh Cells, and Influenza bnAbs: Insights for Improving Universal Vaccine Design GC B细胞、Tfh细胞和流感bnAbs：改进通用疫苗设计的见解

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-07-29 DOI: 10.1111/imr.70153

Takeshi Inoue, Wataru Ise, Tomohiro Kurosaki

引用次数: 0

Counteracting Influenza Virus Evolution Through the Full Spectrum of Broadly Protective Antibodies 通过全谱广泛保护性抗体对抗流感病毒进化。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-07-29 DOI: 10.1111/imr.70147

Yu Adachi, Yoshimasa Takahashi

{"title":"Counteracting Influenza Virus Evolution Through the Full Spectrum of Broadly Protective Antibodies","authors":"Yu Adachi, Yoshimasa Takahashi","doi":"10.1111/imr.70147","DOIUrl":"10.1111/imr.70147","url":null,"abstract":"Despite the presence of licensed vaccines and therapeutics, influenza viruses remain a major public health concern, as they cause seasonal respiratory infections and pose a pandemic threat through the emergence of zoonotic strains. Although neutralizing antibodies elicited by seasonal vaccination constitute a primary defense against infection, their protective capacity is often limited because they frequently target the epitopes that are highly susceptible to structural changes through viral evolution. To overcome this challenge, broadly protective antibodies have been intensively investigated in both humans and animal models. These antibodies recognize conserved epitopes and confer protection through multiple mechanisms beyond conventional neutralization. Recent advances in antibody discovery technologies and structural biology have enabled high-resolution mapping of conserved epitopes and the on-target antibodies that bind them. Furthermore, although broadly protective antibodies are typically elicited only at low frequencies following standard vaccination, several settings have been reported in which their induction is enhanced. Those findings increase the feasibility of epitope-focused vaccine strategies for enhancing the breadth and durability of antibody responses. In this review, we summarize current knowledge of broadly protective flu antibodies and discuss how mechanistic and structural insights can guide the development of next-generation influenza vaccines that offer broad-spectrum protection against antigenically diverse viruses.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"341 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596930","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

Anti-Modified Protein Antibodies in Rheumatoid Arthritis: Pathogenic, Protective, or Passive Bystander? 类风湿关节炎中的抗修饰蛋白抗体：病原性、保护性还是被动旁观者？

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-07-28 DOI: 10.1111/imr.70149

Amber-Sarai F. L. Stalman, Diane van der Woude

{"title":"Anti-Modified Protein Antibodies in Rheumatoid Arthritis: Pathogenic, Protective, or Passive Bystander?","authors":"Amber-Sarai F. L. Stalman, Diane van der Woude","doi":"10.1111/imr.70149","DOIUrl":"10.1111/imr.70149","url":null,"abstract":"The presence of anti-modified protein antibodies (AMPA) is a hallmark of rheumatoid arthritis (RA). AMPA recognize post-translationally modified proteins and are cross-reactive. AMPA include anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies (anti-CarP), and anti-acetylated protein antibodies (AAPA). These autoantibodies can be detected years before disease onset and are associated with disease development and progression. Moreover, AMPA have been associated with genetic and environmental risk factors in RA, including human leukocyte antigen (HLA) alleles, smoking, and microbial exposure. Consequently, AMPA have been implicated in RA pathogenesis, yet their exact role remains unclear. ACPA may exert pathogenic, pro-inflammatory effects through immune complex formation, Fc gamma receptor binding on macrophages, complement activation, and increased neutrophil extracellular trap (NET) formation. Additionally, ACPA have been linked to bone loss and pain induction in mice. However, ACPA may also have protective effects through inhibition of NET release, increased NET clearance, and Fc gamma receptor binding on macrophages. These findings indicate that AMPA may have diverse functions in RA, with both pathogenic and protective effects, whereas some ACPA may not display functional activity. Further studies on AMPA characteristics and mechanisms underlying the pathogenic and protective effects may improve the understanding of the role of AMPA in RA.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"341 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596844","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

The Role of CD4 T Cell Repertoire and Immune Memory Mechanisms in Vaccination and Infection Immunity CD4 T细胞库和免疫记忆机制在疫苗接种和感染免疫中的作用。

IF 10.6 2区医学

Immunological Reviews Pub Date : 2026-07-28 DOI: 10.1111/imr.70148

Masato Kubo

{"title":"The Role of CD4 T Cell Repertoire and Immune Memory Mechanisms in Vaccination and Infection Immunity","authors":"Masato Kubo","doi":"10.1111/imr.70148","DOIUrl":"10.1111/imr.70148","url":null,"abstract":"CD4+ T cells orchestrate adaptive immunity against respiratory viruses through functionally distinct subsets, yet the qualitative differences between vaccine- and infection-induced responses remain incompletely understood. This review summarizes current evidence on how CD4+ T cell subsets shape the magnitude, breadth, and durability of immunity to SARS-CoV-2 and influenza virus. mRNA vaccines elicit a potent Th1/Tfh1-biased response that generates high-affinity neutralizing antibodies and cytotoxic CD4+ T cells (CD4-CTLs) with stem-cell memory properties. However, this strong type I bias may come at the cost of long-term maintenance of humoral memory. Natural infection additionally establishes tissue-resident memory CD4+ T cells (CD4 TRMs) at respiratory mucosal surfaces, providing a frontline defense that current intramuscular vaccines fail to recapitulate efficiently. Crucially, this T cell immunity proves far more resilient than neutralizing antibodies against Variants of Concern, as many memory T cell epitopes from the ancestral strain are conserved across successive variants, a robustness further reinforced by pre-existing cross-reactive CD4+ T cells primed through prior seasonal coronavirus exposure or influenza infection. These observations argue for a fundamental shift in vaccine design toward mucosal delivery and conserved-epitope antigens to achieve durable, broadly cross-reactive protection.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"341 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596922","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