Immunological Reviews最新文献_第2页

Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis. 新出现的炎症小体复合物及其在炎症和脓毒症中的激活和信号传导的分子机制。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 Epub Date: 2024-10-01 DOI: 10.1111/imr.13406

Abhimanu Pandey, Zheyi Li, Manjul Gautam, Aritra Ghosh, Si Ming Man

{"title":"Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis.","authors":"Abhimanu Pandey, Zheyi Li, Manjul Gautam, Aritra Ghosh, Si Ming Man","doi":"10.1111/imr.13406","DOIUrl":"10.1111/imr.13406","url":null,"abstract":"Inflammasomes are multi-protein complexes that assemble within the cytoplasm of mammalian cells in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), driving the secretion of the pro-inflammatory cytokines IL-1β and IL-18, and pyroptosis. The best-characterized inflammasome complexes are the NLRP3, NAIP-NLRC4, NLRP1, AIM2, and Pyrin canonical caspase-1-containing inflammasomes, and the caspase-11 non-canonical inflammasome. Newer inflammasome sensor proteins have been identified, including NLRP6, NLRP7, NLRP9, NLRP10, NLRP11, NLRP12, CARD8, and MxA. These inflammasome sensors can sense PAMPs from bacteria, viruses and protozoa, or DAMPs in the form of mitochondrial damage, ROS, stress and heme. The mechanisms of action, physiological relevance, consequences in human diseases, and avenues for therapeutic intervention for these novel inflammasomes are beginning to be realized. Here, we discuss these emerging inflammasome complexes and their putative activation mechanisms, molecular and signaling pathways, and physiological roles in health and disease.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":"e13406"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337945","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

Role of inflammasomes and neuroinflammation in epilepsy. 炎性体和神经炎症在癫痫中的作用。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 Epub Date: 2024-11-10 DOI: 10.1111/imr.13421

Ava Hollis, John R Lukens

引用次数: 0

Inflammasome-mediated pyroptosis in defense against pathogenic bacteria. 炎症体介导的热蛋白沉积在抵御病原菌的过程中。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 Epub Date: 2024-10-15 DOI: 10.1111/imr.13408

Changhoon Oh, Todd J Spears, Youssef Aachoui

引用次数: 0

MAP Kinase Signaling at the Crossroads of Inflammasome Activation. MAP激酶信号在炎性小体激活的十字路口。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 DOI: 10.1111/imr.13436

Alex Vervaeke, Mohamed Lamkanfi

引用次数: 0

Regulation of the NLRP3 inflammasome by autophagy and mitophagy. 自噬和有丝分裂对 NLRP3 炎症小体的调控。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 Epub Date: 2024-10-17 DOI: 10.1111/imr.13410

Suman Gupta, Suzanne L Cassel, Fayyaz S Sutterwala, Jargalsaikhan Dagvadorj

{"title":"Regulation of the NLRP3 inflammasome by autophagy and mitophagy.","authors":"Suman Gupta, Suzanne L Cassel, Fayyaz S Sutterwala, Jargalsaikhan Dagvadorj","doi":"10.1111/imr.13410","DOIUrl":"10.1111/imr.13410","url":null,"abstract":"The NLRP3 inflammasome is a multiprotein complex that upon activation by the innate immune system drives a broad inflammatory response. The primary initial mediators of this response are pro-IL-1β and pro-IL-18, both of which are in an inactive form. Formation and activation of the NLRP3 inflammasome activates caspase-1, which cleaves pro-IL-1β and pro-IL-18 and triggers the formation of gasdermin D pores. Gasdermin D pores allow for the secretion of active IL-1β and IL-18 initiating the organism-wide inflammatory response. The NLRP3 inflammasome response can be beneficial to the host; however, if the NLRP3 inflammasome is inappropriately activated it can lead to significant pathology. While the primary components of the NLRP3 inflammasome are known, the precise details of assembly and activation are less well defined and conflicting. Here, we discuss several of the proposed pathways of activation of the NLRP3 inflammasome. We examine the role of subcellular localization and the reciprocal regulation of the NLRP3 inflammasome by autophagy. We focus on the roles of mitochondria and mitophagy in activating and regulating the NLRP3 inflammasome. Finally, we detail the impact of pathologic NLRP3 responses in the development and manifestations of pulmonary disease.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":"e13410"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454134","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

Biophysical and Structural Features of αβT-Cell Receptor Mechanosensing: A Paradigmatic Shift in Understanding T-Cell Activation. αβ t细胞受体机械感知的生物物理和结构特征：理解t细胞激活的范式转变。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 Epub Date: 2024-12-29 DOI: 10.1111/imr.13432

Robert J Mallis, Kristine N Brazin, Jonathan S Duke-Cohan, Aoi Akitsu, Hanna M Stephens, Ana C Chang-Gonzalez, Daniel J Masi, Evan H Kirkpatrick, Elizabeth L Holliday, Yinnian Feng, Katarzyna J Zienkiewicz, Jonathan J Lee, Vincenzo Cinella, Kaveri I Uberoy, Kemin Tan, Gerhard Wagner, Haribabu Arthanari, Wonmuk Hwang, Matthew J Lang, Ellis L Reinherz

{"title":"Biophysical and Structural Features of αβT-Cell Receptor Mechanosensing: A Paradigmatic Shift in Understanding T-Cell Activation.","authors":"Robert J Mallis, Kristine N Brazin, Jonathan S Duke-Cohan, Aoi Akitsu, Hanna M Stephens, Ana C Chang-Gonzalez, Daniel J Masi, Evan H Kirkpatrick, Elizabeth L Holliday, Yinnian Feng, Katarzyna J Zienkiewicz, Jonathan J Lee, Vincenzo Cinella, Kaveri I Uberoy, Kemin Tan, Gerhard Wagner, Haribabu Arthanari, Wonmuk Hwang, Matthew J Lang, Ellis L Reinherz","doi":"10.1111/imr.13432","DOIUrl":"10.1111/imr.13432","url":null,"abstract":"αβT cells protect vertebrates against many diseases, optimizing surveillance using mechanical force to distinguish between pathophysiologic cellular alterations and normal self-constituents. The multi-subunit αβT-cell receptor (TCR) operates outside of thermal equilibrium, harvesting energy via physical forces generated by T-cell motility and actin-myosin machinery. When a peptide-bound major histocompatibility complex molecule (pMHC) on an antigen presenting cell is ligated, the αβTCR on the T cell leverages force to form a catch bond, prolonging bond lifetime, and enhancing antigen discrimination. Under load, the αβTCR undergoes reversible structural transitions involving partial unfolding of its clonotypic immunoglobulin-like (Ig) domains and coupled rearrangements of associated CD3 subunits and structural elements. We postulate that transitions provide critical energy to initiate the signaling cascade via induction of αβTCR quaternary structural rearrangements, associated membrane perturbations, exposure of CD3 ITAMs to phosphorylation by non-receptor tyrosine kinases, and phase separation of signaling molecules. Understanding force-mediated signaling by the αβTCR clarifies long-standing questions regarding αβTCR antigen recognition, specificity and affinity, providing a basis for continued investigation. Future directions include examining atomistic mechanisms of αβTCR signal initiation, performance quality, tissue compliance adaptability, and T-cell memory fate. The mechanotransduction paradigm will foster improved rational design of T-cell based vaccines, CAR-Ts, and adoptive therapies.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":"e13432"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913395","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

Z-Nucleic Acid Sensing and Activation of ZBP1 in Cellular Physiology and Disease Pathogenesis. ZBP1在细胞生理和疾病发病中的z -核酸感知和激活。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 DOI: 10.1111/imr.13437

Sanchita Mishra, Ayushi Amin Dey, Sannula Kesavardhana

{"title":"Z-Nucleic Acid Sensing and Activation of ZBP1 in Cellular Physiology and Disease Pathogenesis.","authors":"Sanchita Mishra, Ayushi Amin Dey, Sannula Kesavardhana","doi":"10.1111/imr.13437","DOIUrl":"10.1111/imr.13437","url":null,"abstract":"Z-nucleic acid binding protein 1 (ZBP1) is an innate immune sensor recognizing nucleic acids in Z-conformation. Upon Z-nucleic acid sensing, ZBP1 triggers innate immune activation, inflammation, and programmed cell death during viral infections, mice development, and inflammation-associated diseases. The Zα domains of ZBP1 sense Z-nucleic acids and promote RIP-homotypic interaction motif (RHIM)-dependent signaling complex assembly to mount cell death and inflammation. The studies on ZBP1 spurred an understanding of the role of Z-form RNA and DNA in cellular and physiological functions. In particular, short viral genomic segments, endogenous retroviral elements, and 3'UTR regions are likely sources of Z-RNAs that orchestrate ZBP1 functions. Recent seminal studies identify an intriguing association of ZBP1 with adenosine deaminase acting on RNA-1 (ADAR1), and cyclic GMP-AMP synthase (cGAS) in regulating aberrant nucleic acid sensing, chronic inflammation, and cancer. Thus, ZBP1 is an attractive target to aid the development of specific therapeutic regimes for disease biology. Here, we discuss the role of ZBP1 in Z-RNA sensing, activation of programmed cell death, and inflammation. Also, we discuss how ZBP1 coordinates intracellular perturbations in homeostasis, and Z-nucleic acid formation to regulate chronic diseases and cancer.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"329 1","pages":"e13437"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918831","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

Ketone body metabolism and the NLRP3 inflammasome in Alzheimer's disease. 阿尔茨海默病中的酮体代谢和 NLRP3 炎症体

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 Epub Date: 2024-07-11 DOI: 10.1111/imr.13365

Daniel C Shippy, Abigail H Evered, Tyler K Ulland

{"title":"Ketone body metabolism and the NLRP3 inflammasome in Alzheimer's disease.","authors":"Daniel C Shippy, Abigail H Evered, Tyler K Ulland","doi":"10.1111/imr.13365","DOIUrl":"10.1111/imr.13365","url":null,"abstract":"Alzheimer's disease (AD) is a degenerative brain disorder and the most common form of dementia. AD pathology is characterized by senile plaques and neurofibrillary tangles (NFTs) composed of amyloid-β (Aβ) and hyperphosphorylated tau, respectively. Neuroinflammation has been shown to drive Aβ and tau pathology, with evidence suggesting the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as a key pathway in AD pathogenesis. NLRP3 inflammasome activation in microglia, the primary immune effector cells of the brain, results in caspase-1 activation and secretion of IL-1β and IL-18. Recent studies have demonstrated a dramatic interplay between the metabolic state and effector functions of immune cells. Microglial metabolism in AD is of particular interest, as ketone bodies (acetone, acetoacetate (AcAc), and β-hydroxybutyrate (BHB)) serve as an alternative energy source when glucose utilization is compromised in the brain of patients with AD. Furthermore, reduced cerebral glucose metabolism concomitant with increased BHB levels has been demonstrated to inhibit NLRP3 inflammasome activation. Here, we review the role of the NLRP3 inflammasome and microglial ketone body metabolism in AD pathogenesis. We also highlight NLRP3 inflammasome inhibition by several ketone body therapies as a promising new treatment strategy for AD.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":"e13365"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578431","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

Lessons Learned From Clinical Trials of Immunotherapeutics for COVID-19. 从 COVID-19 免疫疗法临床试验中汲取的经验教训。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 Epub Date: 2024-11-16 DOI: 10.1111/imr.13422

Inyeong Lee, Christopher R Lupfer

{"title":"Lessons Learned From Clinical Trials of Immunotherapeutics for COVID-19.","authors":"Inyeong Lee, Christopher R Lupfer","doi":"10.1111/imr.13422","DOIUrl":"10.1111/imr.13422","url":null,"abstract":"The COVID-19 pandemic caused by the SARS-CoV-2 virus was arguably one of the worst public health disasters of the last 100 years. As many infectious disease experts were focused on influenza, MERS, ZIKA, or Ebola as potential pandemic-causing agents, SARS-CoV-2 appeared to come from nowhere and spread rapidly. As with any zoonotic agent, the initial pathogen was able to transmit to a new host (humans), but it was poorly adapted to the immune environment of the new host and resulted in a maladapted immune response. As the host-pathogen interaction evolved, subsequent variants of SARS-CoV-2 became less pathogenic and acquired immunity in the host provided protection, at least partial protection, to new variants. As the host-pathogen interaction has changed since the beginning of the pandemic, it is possible the clinical results discussed here may not be applicable today as they were at the start of the pandemic. With this caveat in mind, we present an overview of the immune response of severe COVID-19 from a clinical research perspective and examine clinical trials utilizing immunomodulating agents to further elucidate the importance of hyperinflammation as a factor contributing to severe COVID-19 disease.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":" ","pages":"e13422"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643550","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

HLA-E: Immune Receptor Functional Mechanisms Revealed by Structural Studies. HLA-E：结构研究揭示的免疫受体功能机制。

IF 7.5 2区医学

Immunological Reviews Pub Date : 2025-01-01 DOI: 10.1111/imr.13434

Geraldine M Gillespie, Max N Quastel, Andrew J McMichael

{"title":"HLA-E: Immune Receptor Functional Mechanisms Revealed by Structural Studies.","authors":"Geraldine M Gillespie, Max N Quastel, Andrew J McMichael","doi":"10.1111/imr.13434","DOIUrl":"10.1111/imr.13434","url":null,"abstract":"HLA-E is a nonclassical, nonpolymorphic, class Ib HLA molecule. Its primary function is to present a conserved nonamer peptide, termed VL9, derived from the signal sequence of classical MHC molecules to the NKG2x-CD94 receptors on NK cells and a subset of T lymphocytes. These receptors regulate the function of NK cells, and the importance of this role, which is conserved across mammalian species, probably accounts for the lack of genetic polymorphism. A second minor function is to present other, weaker binding, pathogen-derived peptides to T lymphocytes. Most of these peptides bind suboptimally to HLA-E, but this binding appears to be enabled by the relative stability of peptide-free, but receptive, HLA-E-β2m complexes. This, in turn, may favor nonclassical antigen processing that may be associated with bacteria infected cells. This review explores how the structure of HLA-E, bound to different peptides and then to NKG2-CD94 or T-cell receptors, relates to HLA-E cell biology and immunology. A detailed understanding of this molecule could open up opportunities for development of universal T-cell and NK-cell-based immunotherapies.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"329 1","pages":"e13434"},"PeriodicalIF":7.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925939","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