Immunological Reviews最新文献

Established and Emerging Roles of DEAD/H-Box Helicases in Regulating Infection and Immunity. DEAD/H-Box解旋酶在调节感染和免疫中的作用。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1111/imr.13426

Michael Parthun, Matthew E Long, Emily A Hemann

引用次数: 0

The β Common Cytokine Receptor Family Reveals New Functional Paradigms From Structural Complexities. β共同细胞因子受体家族揭示了结构复杂性的新功能范式。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 DOI: 10.1111/imr.13430

Winnie L Kan, Claire M Weekley, Tracy L Nero, Timothy R Hercus, Kwok Ho Yip, Damon J Tumes, Joanna M Woodcock, David M Ross, Daniel Thomas, David Terán, Catherine M Owczarek, Nora W Liu, Luciano G Martelotto, Jose M Polo, Harshita Pant, Denis Tvorogov, Angel F Lopez, Michael W Parker

{"title":"The β Common Cytokine Receptor Family Reveals New Functional Paradigms From Structural Complexities.","authors":"Winnie L Kan, Claire M Weekley, Tracy L Nero, Timothy R Hercus, Kwok Ho Yip, Damon J Tumes, Joanna M Woodcock, David M Ross, Daniel Thomas, David Terán, Catherine M Owczarek, Nora W Liu, Luciano G Martelotto, Jose M Polo, Harshita Pant, Denis Tvorogov, Angel F Lopez, Michael W Parker","doi":"10.1111/imr.13430","DOIUrl":"10.1111/imr.13430","url":null,"abstract":"Cytokines are small proteins that are critical for controlling the growth and activity of hematopoietic cells by binding to cell surface receptors and transmitting signals across membranes. The β common (βc) cytokine receptor family, consisting of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 cytokine receptors, is an architype of the heterodimeric cytokine receptor systems. We now know that signaling by cytokine receptors is not always an \"all or none\" phenomenon. Subtle alterations of the cytokine:receptor complex can result in differential or selective signaling and underpin a variety of diseases including chronic inflammatory conditions and cancers. Structural biology techniques, such as X-ray crystallography and cryo-electron microscopy alongside cell biology studies, are providing detailed insights into cytokine receptor signaling. Recently, we found that the IL-3 receptor ternary complex forms higher-order assemblies, like those found earlier for the GM-CSF receptor, and demonstrated that functionally distinct biological signals arise from different IL-3 receptor oligomeric assemblies. As we enhance our understanding of the structural nuances of cytokine-receptor interactions, we foresee a new era of theranostics whereby structurally guided mechanism-based manipulation of cytokine signaling through rational/targeted protein engineering will harness the full potential of cytokine biology for precision medicine.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"329 1","pages":"e13430"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918830","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

The Evolving T Cell Receptor Recognition Code: The Rules Are More Like Guidelines. 进化中的T细胞受体识别代码：规则更像是指南。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 DOI: 10.1111/imr.13439

George I Gray, P Chukwunalu Chukwuma, Bassant Eldaly, W W J Gihan Perera, Chad A Brambley, Tatiana J Rosales, Brian M Baker

{"title":"The Evolving T Cell Receptor Recognition Code: The Rules Are More Like Guidelines.","authors":"George I Gray, P Chukwunalu Chukwuma, Bassant Eldaly, W W J Gihan Perera, Chad A Brambley, Tatiana J Rosales, Brian M Baker","doi":"10.1111/imr.13439","DOIUrl":"https://doi.org/10.1111/imr.13439","url":null,"abstract":"αβ T cell receptor (TCR) recognition of peptide-MHC complexes lies at the core of adaptive immunity, balancing specificity and cross-reactivity to facilitate effective antigen discrimination. Early structural studies established basic frameworks helpful for understanding and contextualizing TCR recognition and features such as peptide specificity and MHC restriction. However, the growing TCR structural database and studies launched from structural work continue to reveal exceptions to common assumptions and simplifications derived from earlier work. Here we explore our evolving understanding of TCR recognition, illustrating how structural and biophysical investigations regularly uncover complex phenomena that push against paradigms and expand our understanding of how TCRs bind to and discriminate between peptide/MHC complexes. We discuss the implications of these findings for basic, translational, and predictive immunology, including the challenges in accounting for the inherent adaptability, flexibility, and occasional biophysical sloppiness that characterize TCR recognition.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"329 1","pages":"e13439"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968962","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

The Integrin Receptors: From Discovery to Structure to Medicines. 整合素受体：从发现到结构再到药物。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 Epub Date: 2024-12-26 DOI: 10.1111/imr.13433

M Amin Arnaout

{"title":"The Integrin Receptors: From Discovery to Structure to Medicines.","authors":"M Amin Arnaout","doi":"10.1111/imr.13433","DOIUrl":"10.1111/imr.13433","url":null,"abstract":"Innate immune cells perform vital tasks in detecting, seeking, and eliminating invading pathogens, thus ensuring host survival. However, loss of function of these cells or their overactive response to tissue injury often causes serious ailments. It is, therefore, crucial to understand at a basic level how these cells function in health and disease. A major step toward this goal came from studies I conducted in the late 1970s investigating the cause of life-threatening bacterial infections in a pediatric patient. This work led us to trace this disease to the inability of the patient's neutrophils to seek and clear infections due to an inherited deficiency in leukocyte adhesion caused by the loss of a plasma membrane glycoprotein complex now known as CD11/CD18 or β2 integrins. I followed this work by determining the 3-dimensional structures of integrins. These studies provided the foundation for understanding the unique properties of integrins in mediating bidirectional cell adhesion signaling and enabled a structure-guided design of compounds to dial down overactive integrins in common disorders, including thromboinflammatory and autoimmune diseases.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":"e13433"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890724","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 Immunology of SARS-CoV-2. SARS-CoV-2的结构免疫学

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 Epub Date: 2024-12-27 DOI: 10.1111/imr.13431

Meng Yuan, Ian A Wilson

{"title":"Structural Immunology of SARS-CoV-2.","authors":"Meng Yuan, Ian A Wilson","doi":"10.1111/imr.13431","DOIUrl":"10.1111/imr.13431","url":null,"abstract":"The SARS-CoV-2 spike (S) protein has undergone significant evolution, enhancing both receptor binding and immune evasion. In this review, we summarize ongoing efforts to develop antibodies targeting various epitopes of the S protein, focusing on their neutralization potency, breadth, and escape mechanisms. Antibodies targeting the receptor-binding site (RBS) typically exhibit high neutralizing potency but are frequently evaded by mutations in SARS-CoV-2 variants. In contrast, antibodies targeting conserved regions, such as the S2 stem helix and fusion peptide, exhibit broader reactivity but generally lower neutralization potency. However, several broadly neutralizing antibodies have demonstrated exceptional efficacy against emerging variants, including the latest omicron subvariants, underscoring the potential of targeting vulnerable sites such as RBS-A and RBS-D/CR3022. We also highlight public classes of antibodies targeting different sites on the S protein. The vulnerable sites targeted by public antibodies present opportunities for germline-targeting vaccine strategies. Overall, developing escape-resistant, potent antibodies and broadly effective vaccines remains crucial for combating future variants. This review emphasizes the importance of identifying key epitopes and utilizing antibody affinity maturation to inform future therapeutic and vaccine design.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":"e13431"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890721","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

Allosteric Changes Underlie the Outside-In Transmission of Activatory Signals in the TCR. 变构变化是TCR中激活信号由外向内传递的基础。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 DOI: 10.1111/imr.13438

Balbino Alarcon, Wolfgang W Schamel

{"title":"Allosteric Changes Underlie the Outside-In Transmission of Activatory Signals in the TCR.","authors":"Balbino Alarcon, Wolfgang W Schamel","doi":"10.1111/imr.13438","DOIUrl":"10.1111/imr.13438","url":null,"abstract":"Rather than being contained in a single polypeptide, and unlike receptor tyrosine kinases, the T cell receptor (TCR) divides its signaling functions among its subunits: TCRα/β bind the extracellular ligand, an antigenic peptide-MHC complex (pMHC), and the CD3 subunits (CD3γ, CD3δ, CD3ε, and CD3ζ) transmit this information to the cytoplasm. How information about the quality of pMHC binding outside is transmitted to the cytoplasm remains a matter of debate. In this review, we compile data generated using a wide variety of experimental systems indicating that TCR engagement by an appropriate pMHC triggers allosteric changes transmitted from the ligand-binding loops in the TCRα and TCRβ subunits to the cytoplasmic tails of the CD3 subunits. We summarize how pMHC and stimulatory antibody binding to TCR ectodomains induces the exposure of a polyproline sequence in the CD3ε cytoplasmic tail for binding to the Nck adapter, the exposure of the RK motif in CD3ε for recruiting the Lck tyrosine kinase, and the induced exposure and phosphorylation of tyrosine residues in all the CD3 cytoplasmic tails. We also review the yet incipient data that help elucidate the structural basis of the Active and Resting conformations of the TCR.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"329 1","pages":"e13438"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925938","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

DNA sensors in metabolic and cardiovascular diseases: Molecular mechanisms and therapeutic prospects. 代谢和心血管疾病中的 DNA 传感器：分子机制和治疗前景。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 Epub Date: 2024-08-19 DOI: 10.1111/imr.13382

Hyosang Kwak, Ein Lee, Rajendra Karki

{"title":"DNA sensors in metabolic and cardiovascular diseases: Molecular mechanisms and therapeutic prospects.","authors":"Hyosang Kwak, Ein Lee, Rajendra Karki","doi":"10.1111/imr.13382","DOIUrl":"10.1111/imr.13382","url":null,"abstract":"DNA sensors generally initiate innate immune responses through the production of type I interferons. While extensively studied for host defense against invading pathogens, emerging evidence highlights the involvement of DNA sensors in metabolic and cardiovascular diseases. Elevated levels of modified, damaged, or ectopically localized self-DNA and non-self-DNA have been observed in patients and animal models with obesity, diabetes, fatty liver disease, and cardiovascular disease. The accumulation of cytosolic DNA aberrantly activates DNA signaling pathways, driving the pathological progression of these disorders. This review highlights the roles of specific DNA sensors, such as cyclic AMP-GMP synthase and stimulator of interferon genes (cGAS-STING), absent in melanoma 2 (AIM2), toll-like receptor 9 (TLR9), interferon gamma-inducible protein 16 (IFI16), DNA-dependent protein kinase (DNA-PK), and DEAD-box helicase 41 (DDX41) in various metabolic disorders. We explore how DNA signaling pathways in both immune and non-immune cells contribute to the development of these diseases. Furthermore, we discuss the intricate interplay between metabolic stress and immune responses, offering insights into potential therapeutic targets for managing metabolic and cardiovascular disorders. Understanding the mechanisms of DNA sensor signaling in these contexts provides a foundation for developing novel interventions aimed at mitigating the impact of these pervasive health issues.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":"e13382"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999065","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

Balanced regulation of ROS production and inflammasome activation in preventing early development of colorectal cancer. 平衡调节 ROS 生成和炎性体激活，预防结直肠癌的早期发展。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 Epub Date: 2024-11-10 DOI: 10.1111/imr.13417

Longjun Li, Tao Xu, Xiaopeng Qi

{"title":"Balanced regulation of ROS production and inflammasome activation in preventing early development of colorectal cancer.","authors":"Longjun Li, Tao Xu, Xiaopeng Qi","doi":"10.1111/imr.13417","DOIUrl":"10.1111/imr.13417","url":null,"abstract":"Reactive oxygen species (ROS) production and inflammasome activation are the key components of the innate immune response to microbial infection and sterile insults. ROS are at the intersection of inflammation and immunity during cancer development. Balanced regulation of ROS production and inflammasome activation serves as the central hub of innate immunity, determining whether a cell will survive or undergo cell death. However, the mechanisms underlying this balanced regulation remain unclear. Mitochondria and NADPH oxidases are the two major sources of ROS production. Recently, NCF4, a component of the NADPH oxidase complex that primarily contributes to ROS generation in phagocytes, was reported to balance ROS production and inflammasome activation in macrophages. The phosphorylation and puncta distribution of NCF4 shifts from the membrane-bound NADPH complex to the perinuclear region, promoting ASC speck formation and inflammasome activation, which triggers downstream IL-18-IFN-γ signaling to prevent the progression of colorectal cancer (CRC). Here, we review ROS signaling and inflammasome activation studies in colitis-associated CRC and propose that NCF4 acts as a ROS sensor that balances ROS production and inflammasome activation. In addition, NCF4 is a susceptibility gene for Crohn's disease (CD) and CRC. We discuss the evidence demonstrating NCF4's crucial role in facilitating cell-cell contact between immune cells and intestinal cells, and mediating the paracrine effects of inflammatory cytokines and ROS. This coordination of the signaling network helps create a robust immune microenvironment that effectively prevents epithelial cell mutagenesis and tumorigenesis during the early stage of colitis-associated CRC.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":"e13417"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612331","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

Recognition of Self and Viral Ligands by NK Cell Receptors. NK细胞受体对自身和病毒配体的识别。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 DOI: 10.1111/imr.13435

Roy A Mariuzza, Pragya Singh, Sharanbasappa S Karade, Salman Shahid, Vijay Kumar Sharma

{"title":"Recognition of Self and Viral Ligands by NK Cell Receptors.","authors":"Roy A Mariuzza, Pragya Singh, Sharanbasappa S Karade, Salman Shahid, Vijay Kumar Sharma","doi":"10.1111/imr.13435","DOIUrl":"10.1111/imr.13435","url":null,"abstract":"Natural killer (NK) cells are essential elements of the innate immune response against tumors and viral infections. NK cell activation is governed by NK cell receptors that recognize both cellular (self) and viral (non-self) ligands, including MHC, MHC-related, and non-MHC molecules. These diverse receptors belong to two distinct structural families, the C-type lectin superfamily and the immunoglobulin superfamily. NK receptors include Ly49s, KIRs, LILRs, and NKG2A/CD94, which bind MHC class I (MHC-I) molecules, and NKG2D, which binds MHC-I paralogs such MICA and ULBP. Other NK receptors recognize tumor-associated antigens (NKp30, NKp44, NKp46), cell-cell adhesion proteins (KLRG1, CD96), or genetically coupled C-type lectin-like ligands (NKp65, NKR-P1). Additionally, cytomegaloviruses have evolved various immunoevasins, such as m157, m12, and UL18, which bind NK receptors and act as decoys to enable virus-infected cells to escape NK cell-mediated lysis. We review the remarkable progress made in the past 25 years in determining structures of representatives of most known NK receptors bound to MHC, MHC-like, and non-MHC ligands. Together, these structures reveal the multiplicity of solutions NK receptors have developed to recognize these molecules, and thereby mediate crucial interactions for regulating NK cytolytic activity by self and viral ligands.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"329 1","pages":"e13435"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918829","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

From fat to fire: The lipid-inflammasome connection. 从脂肪到火焰脂质-炎症体之间的联系

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 Epub Date: 2024-09-27 DOI: 10.1111/imr.13403

Paras K Anand

{"title":"From fat to fire: The lipid-inflammasome connection.","authors":"Paras K Anand","doi":"10.1111/imr.13403","DOIUrl":"10.1111/imr.13403","url":null,"abstract":"Inflammasomes are multiprotein complexes that play a crucial role in regulating immune responses by governing the activation of Caspase-1, the secretion of pro-inflammatory cytokines, and the induction of inflammatory cell death, pyroptosis. The inflammasomes are pivotal in effective host defense against a range of pathogens. Yet, overt activation of inflammasome signaling can be detrimental. The most well-studied NLRP3 inflammasome has the ability to detect a variety of stimuli including pathogen-associated molecular patterns, environmental irritants, and endogenous stimuli released from dying cells. Additionally, NLRP3 acts as a key sensor of cellular homeostasis and can be activated by disturbances in diverse metabolic pathways. Consequently, NLRP3 is considered a key player linking metabolic dysregulation to numerous inflammatory disorders such as gout, diabetes, and atherosclerosis. Recently, compelling studies have highlighted a connection between lipids and the regulation of NLRP3 inflammasome. Lipids are integral to cellular processes that serve not only in maintaining the structural integrity and subcellular compartmentalization, but also in contributing to physiological equilibrium. Certain lipid species are known to define NLRP3 subcellular localization, therefore directly influencing the site of inflammasome assembly and activation. For instance, phosphatidylinositol 4-phosphate plays a crucial role in NLRP3 localization to the trans Golgi network. Moreover, new evidence has demonstrated the roles of lipid biosynthesis and trafficking in activation of the NLRP3 inflammasome. This review summarizes and discusses these emerging and varied roles of lipid metabolism in inflammasome activation. A deeper understanding of lipid-inflammasome interactions may open new avenues for therapeutic interventions to prevent or treat chronic inflammatory and autoimmune conditions.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":"e13403"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337943","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