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Using structure-function information from IFN-γ-binding proteins and biased agonists to uncouple immunostimulatory and immunosuppressive activities.
IF 13.1 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-18 DOI: 10.1016/j.it.2025.02.013
Lucas Mendes-Monteiro, Abel Viejo-Borbolla

IFN-γ is a pleiotropic antiviral cytokine that coordinates innate and adaptive immune responses and induces both immunostimulatory and immunosuppressive activities, limiting its use in the clinic. Due to its antiviral role, several viruses express proteins that bind IFN-γ, blocking its interaction with the IFN-γ receptor (IFNGR). However, varicella zoster virus glycoprotein C binds IFN-γ and induces the expression of a subset of specific ISGs, similar to biased IFN-γ agonists generated based on the crystal structure of the IFN-γ - IFNGR complex. Here, we propose using structural and mechanistic information from viral proteins and biased agonists to design novel IFN-γ agonists that fine-tune IFN-γ - IFNGR activity, reducing the immunosuppressive and toxic effects of this cytokine.

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引用次数: 0
On tending sprouts: empowering emerging immunologists in Latin America.
IF 13.1 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-05 DOI: 10.1016/j.it.2025.02.006
Marion E G Brunck, Maria Julia Lamberti, Anne M Hahn

Supporting emerging immunologists in Latin America and the Caribbean (LAC) is crucial amidst fragile funding and policy shifts in the region. Their growth can deliver region-specific health solutions, foster pandemic preparedness, and advance neglected tropical disease research, paying it forward to reduce health inequities and drive global scientific progress.

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引用次数: 0
Insights into palmitoylation-mediated regulation of inflammasomes.
IF 13.1 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-05 DOI: 10.1016/j.it.2025.02.008
Qiwei Jiang, Lang Bu, Jianping Guo

The mammalian inflammasome is crucial for responding to environmental/intrinsic stress, and its regulation remains a significant focus in immune-mediated inflammatory diseases and antitumor immunity. Recent studies highlight a close link between palmitoylation and inflammasome regulation. However, this type of regulation remains elusive but may harbor potential for combating inflammation-driven disorders.

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引用次数: 0
Novel insights and recent progress in osteoimmunology.
IF 13.1 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-01 Epub Date: 2025-02-25 DOI: 10.1016/j.it.2025.02.003
Iannis E Adamopoulos, Yongwon Choi, Hiroshi Takayanagi

Osteoimmunology is an interdisciplinary branch of immunology studying bidirectional interactions between the immune and skeletal systems. Bone marrow is vital for the production of immune cells and is implicated in multiple diseases across all immunology disciplines. Here, we briefly discuss recent progress from the past 5 years in the field and how it impacts our current understanding of health and disease.

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引用次数: 0
Complement: you gutsy thing!: (Trends in Immunology 45, 228-230; 2024).
IF 13.1 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-01 Epub Date: 2025-02-15 DOI: 10.1016/j.it.2025.02.001
Claudia Kemper
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引用次数: 0
Rest and rinse: sleeping rhythms drive brain detox.
IF 13.1 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-01 Epub Date: 2025-02-28 DOI: 10.1016/j.it.2025.02.007
Leon C D Smyth, Benjamin A Plog, Jonathan Kipnis

Sleep is a major driver of waste clearance from the brain, but the mechanisms underpinning brain cleansing during sleep, which are also important for immunological functions, are poorly understood. Recent mouse work by Hauglund et al. shows how oscillatory surges in norepinephrine (NE) during sleep drive vascular pulsation and cerebrospinal fluid (CSF) movement to cleanse the brain.

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引用次数: 0
Extracellular vesicles transport gasdermin pores, amplifying inflammatory cell death.
IF 13.1 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-01 Epub Date: 2025-02-26 DOI: 10.1016/j.it.2025.02.004
Bhesh Raj Sharma, Thirumala-Devi Kanneganti

Lytic cell death is crucial for antimicrobial and antitumor immunity; however, unchecked pyroptosis drives pathology in sepsis. Wright et al. demonstrate that widespread cell death following pyroptosis is propagated by extracellular vesicles (EVs) carrying gasdermin D (GSDMD) pores that become integrated into the membrane of neighboring cells, driving inflammatory cell death.

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引用次数: 0
Monoallelic expression in human immune cells: linking genotype to phenotype.
IF 13.1 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-01 Epub Date: 2025-03-12 DOI: 10.1016/j.it.2025.02.005
Lennart Hammarström, Qiang Pan-Hammarström

Patients with an inborn error of immunity (IEI) often show a complete penetrance of their disease-causing mutation, whereas other forms of IEI show a family pattern where many family members carrying the same mutation remain unaffected. The underlying mechanism, differential allele-specific expression, was recently and elegantly demonstrated by Stewart et al.

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引用次数: 0
New thoughts on the gut-immune axis of arthritis.
IF 13.1 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-01 Epub Date: 2025-03-10 DOI: 10.1016/j.it.2025.01.006
Alexandra Thiran, Lars Vereecke

Arthritis is associated with varying degrees of intestinal inflammation and microbiota dysbiosis, leading to the 'gut-joint axis hypothesis' in which intestinal and joint inflammation are suggested to be interconnected through immune-microbiota interactions. While clinical observations support this, causality remains uncertain. Rodent models have provided insights into potential mechanisms by uncovering microbial influences and immune pathways that either connect or uncouple gut and joint inflammation. Based on recent findings, we propose the 'immune hypersensitivity hypothesis' whereby central immune hyper-reactivity can independently drive joint inflammation via local sterile triggers, and gut inflammation via microbial triggers. We argue that this suggests a more nuanced role of the microbiota in arthritis pathogenesis that varies according to the predominant immune mechanisms in disease subtypes. We explore gut-immune interactions in arthritis, highlight ongoing challenges, and propose future research directions.

关节炎与不同程度的肠道炎症和微生物群失调有关,由此产生了 "肠道-关节轴假说",即肠道炎症和关节炎症通过免疫-微生物群相互作用而相互关联。虽然临床观察支持这一观点,但因果关系仍不确定。啮齿动物模型揭示了微生物的影响和免疫途径,从而揭示了肠道和关节炎症之间的潜在机制。根据最近的研究结果,我们提出了 "免疫超敏假说",即中枢免疫过度反应可通过局部无菌诱因独立驱动关节炎症,并通过微生物诱因驱动肠道炎症。我们认为,这表明微生物群在关节炎发病机制中的作用更加微妙,这种作用因疾病亚型的主要免疫机制而异。我们探讨了关节炎中肠道与免疫的相互作用,强调了当前面临的挑战,并提出了未来的研究方向。
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引用次数: 0
Metabolic and stress response adaptations in T cells to fever and physiological heat.
IF 13.1 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-01 Epub Date: 2025-02-20 DOI: 10.1016/j.it.2025.01.007
Benjamin A Wilander, Jeffrey C Rathmell

Fevers are an ancient feature of the inflammatory microenvironment. While fevers may improve the immune response to pathogens, mechanisms are unclear. We explore recent studies of how fever-range temperatures inform mammalian T cell metabolism, differentiation, and stress responses. Recent evidence indicates that metabolic programs initiated by fever are maintained upon return to thermo-normality, potentially providing a lasting benefit. Despite its impact, temperature remains overlooked and warrants further study. This is especially apparent when considering the wide temperature differential between tissues within the body and during inflammatory disease progression. We propose that differences in the metabolic and stress responses between T cell subsets upon thermal stress contribute to determining immune cell makeup and fate during inflammation.

{"title":"Metabolic and stress response adaptations in T cells to fever and physiological heat.","authors":"Benjamin A Wilander, Jeffrey C Rathmell","doi":"10.1016/j.it.2025.01.007","DOIUrl":"10.1016/j.it.2025.01.007","url":null,"abstract":"<p><p>Fevers are an ancient feature of the inflammatory microenvironment. While fevers may improve the immune response to pathogens, mechanisms are unclear. We explore recent studies of how fever-range temperatures inform mammalian T cell metabolism, differentiation, and stress responses. Recent evidence indicates that metabolic programs initiated by fever are maintained upon return to thermo-normality, potentially providing a lasting benefit. Despite its impact, temperature remains overlooked and warrants further study. This is especially apparent when considering the wide temperature differential between tissues within the body and during inflammatory disease progression. We propose that differences in the metabolic and stress responses between T cell subsets upon thermal stress contribute to determining immune cell makeup and fate during inflammation.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":"195-205"},"PeriodicalIF":13.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473212","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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Trends in Immunology
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