Pub Date : 2025-03-18DOI: 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.
{"title":"Using structure-function information from IFN-γ-binding proteins and biased agonists to uncouple immunostimulatory and immunosuppressive activities.","authors":"Lucas Mendes-Monteiro, Abel Viejo-Borbolla","doi":"10.1016/j.it.2025.02.013","DOIUrl":"https://doi.org/10.1016/j.it.2025.02.013","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659679","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}
Pub Date : 2025-03-05DOI: 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.
{"title":"On tending sprouts: empowering emerging immunologists in Latin America.","authors":"Marion E G Brunck, Maria Julia Lamberti, Anne M Hahn","doi":"10.1016/j.it.2025.02.006","DOIUrl":"https://doi.org/10.1016/j.it.2025.02.006","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574723","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}
Pub Date : 2025-03-05DOI: 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.
{"title":"Insights into palmitoylation-mediated regulation of inflammasomes.","authors":"Qiwei Jiang, Lang Bu, Jianping Guo","doi":"10.1016/j.it.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.it.2025.02.008","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574721","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}
Pub Date : 2025-03-01Epub Date: 2025-02-25DOI: 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.
{"title":"Novel insights and recent progress in osteoimmunology.","authors":"Iannis E Adamopoulos, Yongwon Choi, Hiroshi Takayanagi","doi":"10.1016/j.it.2025.02.003","DOIUrl":"10.1016/j.it.2025.02.003","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":"192-194"},"PeriodicalIF":13.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517311","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}
Pub Date : 2025-03-01Epub Date: 2025-02-15DOI: 10.1016/j.it.2025.02.001
Claudia Kemper
{"title":"Complement: you gutsy thing!: (Trends in Immunology 45, 228-230; 2024).","authors":"Claudia Kemper","doi":"10.1016/j.it.2025.02.001","DOIUrl":"10.1016/j.it.2025.02.001","url":null,"abstract":"","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":"258"},"PeriodicalIF":13.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433940","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}
Pub Date : 2025-03-01Epub Date: 2025-02-28DOI: 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.
{"title":"Rest and rinse: sleeping rhythms drive brain detox.","authors":"Leon C D Smyth, Benjamin A Plog, Jonathan Kipnis","doi":"10.1016/j.it.2025.02.007","DOIUrl":"10.1016/j.it.2025.02.007","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":"189-191"},"PeriodicalIF":13.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538175","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}
Pub Date : 2025-03-01Epub Date: 2025-02-26DOI: 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.
{"title":"Extracellular vesicles transport gasdermin pores, amplifying inflammatory cell death.","authors":"Bhesh Raj Sharma, Thirumala-Devi Kanneganti","doi":"10.1016/j.it.2025.02.004","DOIUrl":"10.1016/j.it.2025.02.004","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":"183-185"},"PeriodicalIF":13.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525275","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}
Pub Date : 2025-03-01Epub Date: 2025-03-12DOI: 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.
{"title":"Monoallelic expression in human immune cells: linking genotype to phenotype.","authors":"Lennart Hammarström, Qiang Pan-Hammarström","doi":"10.1016/j.it.2025.02.005","DOIUrl":"10.1016/j.it.2025.02.005","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":"186-188"},"PeriodicalIF":13.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626809","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}
Pub Date : 2025-03-01Epub Date: 2025-03-10DOI: 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.
{"title":"New thoughts on the gut-immune axis of arthritis.","authors":"Alexandra Thiran, Lars Vereecke","doi":"10.1016/j.it.2025.01.006","DOIUrl":"10.1016/j.it.2025.01.006","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":"206-218"},"PeriodicalIF":13.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607102","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}
Pub Date : 2025-03-01Epub Date: 2025-02-20DOI: 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}