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Reframing IL-27: a central regulator of CD8+ T cell immunity. 重组IL-27: CD8+ T细胞免疫的中枢调节因子
IF 13.9 1区 医学
Trends in Immunology Pub Date : 2026-04-01 Epub Date: 2025-11-20 DOI: 10.1016/j.it.2025.10.012
Valentina Venzin, Matteo Iannacone
{"title":"Reframing IL-27: a central regulator of CD8<sup>+</sup> T cell immunity.","authors":"Valentina Venzin, Matteo Iannacone","doi":"10.1016/j.it.2025.10.012","DOIUrl":"10.1016/j.it.2025.10.012","url":null,"abstract":"<p><p>Interleukin-27 (IL-27), a member of the IL-12 cytokine family, was long viewed primarily as a regulator of CD4<sup>+</sup> T cell immunity. Subsequent studies revealed that IL-27 also directly modulates CD8<sup>+</sup> T cells, displaying both stimulatory and inhibitory potential. Recent work extends this earlier literature, showing that IL-27 in infection and cancer can promote effector differentiation, sustain survival, and reverse dysfunction, often without the systemic toxicity associated with related cytokines. This review outlines the molecular features, signaling mechanisms, and cellular sources of IL-27, integrating emerging evidence from viral, tumor, and autoimmune settings. We propose that IL-27 operates not as an inherently pro- or anti-inflammatory cytokine but as a context-dependent tuner of CD8<sup>+</sup> T cell cytotoxic immunity, offering new opportunities for therapeutic exploitation.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":"272-283"},"PeriodicalIF":13.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Cell intrinsic versus cell extrinsic control of plasma cell longevity. 浆细胞寿命的细胞内在与细胞外在控制。
IF 13.9 1区 医学
Trends in Immunology Pub Date : 2026-04-01 Epub Date: 2025-11-24 DOI: 10.1016/j.it.2025.10.013
David M Allman, Avinash Bhandoola
{"title":"Cell intrinsic versus cell extrinsic control of plasma cell longevity.","authors":"David M Allman, Avinash Bhandoola","doi":"10.1016/j.it.2025.10.013","DOIUrl":"10.1016/j.it.2025.10.013","url":null,"abstract":"<p><p>The maintenance of serum antibodies requires the persistence of plasma cells within the bone marrow (BM). However, little is understood about why relatively few BM plasma cells live for extended periods. We consider two opposing viewpoints. We first consider the notion that sustained antibody titers requires localization of plasma cells to specialized BM niches where they access cell extrinsic survival factors, including extracellular ATP (eATP). We then consider the alternative possibility that plasma cell survival requires optimized cell intrinsic control of antibody synthesis supported by eATP stimulation of purinergic receptors. Based on the latter view we propose that many BM plasma cells fail to achieve maximal longevity due to suboptimal protein homeostasis rather than compromised access to cell extrinsic survival cues.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":"262-271"},"PeriodicalIF":13.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Tumor-derived cystatin C enables amyloid clearance. 肿瘤源性胱抑素C能够清除淀粉样蛋白。
IF 13.9 1区 医学
Trends in Immunology Pub Date : 2026-04-01 Epub Date: 2026-03-11 DOI: 10.1016/j.it.2026.02.007
Joseph Zambelas, Yun Huang, Hong Zhao, Stephen T C Wong
{"title":"Tumor-derived cystatin C enables amyloid clearance.","authors":"Joseph Zambelas, Yun Huang, Hong Zhao, Stephen T C Wong","doi":"10.1016/j.it.2026.02.007","DOIUrl":"10.1016/j.it.2026.02.007","url":null,"abstract":"<p><p>Li et al. described a tumor-derived neuroimmune mechanism that promotes clearance of established amyloid pathology in Alzheimer's disease. secreted cystatin C activates TREM2-dependent microglial phagocytosis, reducing plaques and improving cognition. This work introduces a context-dependent neuroimmune-modulatory strategy that shifts Alzheimer's therapy from broad immune activation toward substrate-coupled amyloid clearance.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":"246-248"},"PeriodicalIF":13.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147445721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 dual-adjuvant logic of mRNA vaccines. mRNA疫苗的双佐剂逻辑。
IF 13.9 1区 医学
Trends in Immunology Pub Date : 2026-04-01 Epub Date: 2026-03-18 DOI: 10.1016/j.it.2026.01.012
R Dilshan Malewana, Kizzmekia S Corbett-Helaire
{"title":"The dual-adjuvant logic of mRNA vaccines.","authors":"R Dilshan Malewana, Kizzmekia S Corbett-Helaire","doi":"10.1016/j.it.2026.01.012","DOIUrl":"10.1016/j.it.2026.01.012","url":null,"abstract":"<p><p>Deciphering how mRNA vaccines generate humoral immunity could accelerate next-generation vaccine design. Castaño et al. reveal that mRNA-lipid nanoparticle vaccines employ a dual-adjuvant mechanism: nucleoside-modified mRNA triggers type I interferons to mature dendritic cells, while lipid nanoparticles induce a pro-T follicular helper cell program, together promoting robust germinal center responses.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":"243-245"},"PeriodicalIF":13.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147488304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Targeting TLR2 agonists as immunomodulators with broad antiviral activity. 靶向TLR2激动剂作为具有广泛抗病毒活性的免疫调节剂。
IF 13.9 1区 医学
Trends in Immunology Pub Date : 2026-04-01 DOI: 10.1016/j.it.2026.03.003
Nongthombam Boby, Bapi Pahar
{"title":"Targeting TLR2 agonists as immunomodulators with broad antiviral activity.","authors":"Nongthombam Boby, Bapi Pahar","doi":"10.1016/j.it.2026.03.003","DOIUrl":"https://doi.org/10.1016/j.it.2026.03.003","url":null,"abstract":"<p><p>Toll-like receptor-2 (TLR2) serves as an innate immune sensor that recognizes specific viral proteins, thereby initiating signaling pathways that can either enhance antiviral host defenses or induce pathological inflammatory responses. In this forum, we discuss the role of TLR2 and its agonists in enhancing antiviral and vaccine-induced immune responses.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Decoding brain border immunity to enable future therapeutic avenues. 破解脑边界免疫，为未来的治疗提供途径。
IF 13.9 1区 医学
Trends in Immunology Pub Date : 2026-04-01 Epub Date: 2026-01-08 DOI: 10.1016/j.it.2025.12.007
Lien Van Hoecke, Lore Van Acker, Roosmarijn E Vandenbroucke
{"title":"Decoding brain border immunity to enable future therapeutic avenues.","authors":"Lien Van Hoecke, Lore Van Acker, Roosmarijn E Vandenbroucke","doi":"10.1016/j.it.2025.12.007","DOIUrl":"10.1016/j.it.2025.12.007","url":null,"abstract":"<p><p>The brain is no longer viewed as immunologically isolated but as an organ surrounded by dynamic border compartments that coordinate surveillance, drainage, and communication with the periphery. Key interfaces - including the meninges, blood-brain barrier, choroid plexus (ChP), and skull bone marrow - host specialized immune niches that regulate antigen sampling, leukocyte trafficking, and neuroimmune signaling. Recent advances in imaging and in single-cell and spatial profiling have revealed previously unrecognized cell types, migration routes, and barrier specializations that shape central nervous system (CNS) immunity in health and disease. Understanding how these border tissues sense, integrate, and modulate immune activity opens opportunities for therapeutically tuning neuroimmune responses at the brain's periphery while preserving parenchymal integrity.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":"320-336"},"PeriodicalIF":13.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145946550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Endothelial cells modulate immune cell responses during atherosclerosis. 动脉粥样硬化期间内皮细胞调节免疫细胞反应。
IF 13.9 1区 医学
Trends in Immunology Pub Date : 2026-03-31 DOI: 10.1016/j.it.2026.03.001
Sanne van Kesteren, Lisa Smeehuijzen, Robert Stevenson, Jeffrey Kroon
{"title":"Endothelial cells modulate immune cell responses during atherosclerosis.","authors":"Sanne van Kesteren, Lisa Smeehuijzen, Robert Stevenson, Jeffrey Kroon","doi":"10.1016/j.it.2026.03.001","DOIUrl":"https://doi.org/10.1016/j.it.2026.03.001","url":null,"abstract":"<p><p>Endothelial cells (ECs), which form the monolayer lining the vasculature, serve as critical gatekeepers of vascular homeostasis. They actively coordinate immune cell recruitment, adhesion, migration, and activation. Through tightly controlled expression and secretion of chemokines, cytokines, adhesion molecules, and immunomodulatory proteins, ECs locally orchestrate immune responses. In atherosclerosis, ECs contribute to plaque formation, plaque instability, and local inflammation by facilitating immune cell activation and transmigration into the plaque. However, ECs are highly heterogeneous, with their phenotype and function influenced by vascular localization and disease stage. EC subpopulations are transcriptionally distinct and adopt to either proinflammatory or angiogenic phenotypes and differentially participate in immune modulation. This review discusses recent insights into the immunomodulatory functions of ECs in atherosclerosis and underscores the importance of EC heterogeneity in understanding endothelial-immune cell interactions.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
THEMIS: new insights into its evolution, structure, and function. 忒弥斯：对其演化、结构和功能的新见解。
IF 13.9 1区 医学
Trends in Immunology Pub Date : 2026-03-31 DOI: 10.1016/j.it.2026.02.006
Avik Dutta, L Aravind, Seeyoung Choi, Renaud Lesourne, Paul E Love
{"title":"THEMIS: new insights into its evolution, structure, and function.","authors":"Avik Dutta, L Aravind, Seeyoung Choi, Renaud Lesourne, Paul E Love","doi":"10.1016/j.it.2026.02.006","DOIUrl":"https://doi.org/10.1016/j.it.2026.02.006","url":null,"abstract":"<p><p>THEMIS (thymocyte-expressed molecule involved in selection) is the founding member of a family of metazoan proteins distinguished by the presence of a novel structural element designated the cysteine-containing all-beta-in-THEMIS (CABIT) module. Several studies have confirmed a critical role for THEMIS in T cell antigen receptor (TCR) signaling during T cell development, and more recent work has shown an important role for THEMIS in peripheral T cells. However, the molecular function of THEMIS in the TCR signaling pathway has long remained controversial due to conflicting experimental results. In this review article, we summarize recent data that provide new insights into the structure, evolution, and broader roles of the CABIT module, as well as clarify the molecular mechanism by which THEMIS influences TCR and cytokine receptor signaling in developing and mature T cells.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Redefining nucleotide-binding oligomerization domain-like receptors: from immune sentinels to multifunctional regulators. 重新定义核苷酸结合寡聚化结构域样受体：从免疫哨兵到多功能调节剂。
IF 13.9 1区 医学
Trends in Immunology Pub Date : 2026-03-28 DOI: 10.1016/j.it.2026.03.004
Suhyun Kim, Sehee Park, SangJoon Lee
{"title":"Redefining nucleotide-binding oligomerization domain-like receptors: from immune sentinels to multifunctional regulators.","authors":"Suhyun Kim, Sehee Park, SangJoon Lee","doi":"10.1016/j.it.2026.03.004","DOIUrl":"https://doi.org/10.1016/j.it.2026.03.004","url":null,"abstract":"<p><p>Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are a large family of intracellular pattern recognition receptors primarily involved in innate immunity. Although canonical inflammasome-forming NLRs, such as NLRP3 and NLRC4, and microbial sensors, including NOD1 and NOD2, are well-characterized, the functions of many other NLRs remain poorly understood. This review article addresses this gap by highlighting the critical, context-dependent roles of these less-characterized NLRs beyond pathogen sensing. We classify these NLRs as immune modulators, regulators of autophagy and mitophagy, tissue-specific effectors, and reproductive mediators, expanding the traditional view of NLR functions. Understanding the diverse, context-dependent roles of NLRs across biological systems is essential to fully understand their complex regulatory networks and therapeutic potential, which extends beyond classical inflammasome functions.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Seven subsets, two fates: mouse γδ T cells in cancer immunity. 七个亚群，两个命运：小鼠γδ T细胞在癌症免疫中的作用。
IF 13.9 1区 医学
Trends in Immunology Pub Date : 2026-03-27 DOI: 10.1016/j.it.2026.02.009
Abhiram C T Mallu, Natalie Z Phinney, Federico Lupo, Seth B Coffelt
{"title":"Seven subsets, two fates: mouse γδ T cells in cancer immunity.","authors":"Abhiram C T Mallu, Natalie Z Phinney, Federico Lupo, Seth B Coffelt","doi":"10.1016/j.it.2026.02.009","DOIUrl":"https://doi.org/10.1016/j.it.2026.02.009","url":null,"abstract":"<p><p>The importance of γδ T cells in cancer, as defenders against tumorigenesis, was established more than 2 decades ago. Since that time, research using mouse models of cancer has brought to light a nonuniform view of tumor-associated γδ T cells by providing granularity into the role of individual γδ T cell subsets in specific cancer types. In this review, we discuss data that highlight the unique contributions of Vγ1<sup>+</sup>, Vγ4<sup>+</sup>, Vγ5<sup>+</sup>, Vγ6<sup>+</sup>, and Vγ7<sup>+</sup> cells throughout cancer progression. We delve into their responses to tumors, including both protective and pathogenic functions. We examine how the mechanisms by which these mouse immune cell subsets shape tumor development and spread can be exploited for therapeutic purposes in people with cancer.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
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