Nature Reviews Rheumatology最新文献

{"title":"Insights into chondrocyte populations in cartilaginous tissues at the single-cell level","authors":"Csaba Matta, Roland Takács, Mona Dvir-Ginzberg, Stephen M. Richardson, Karoliina Pelttari, Girish Pattappa, Makarand V. Risbud, Ali Mobasheri","doi":"10.1038/s41584-025-01275-0","DOIUrl":"10.1038/s41584-025-01275-0","url":null,"abstract":"Chondrocyte biology is being revolutionized by single-cell multi-omics technologies, revealing cellular heterogeneity within cartilaginous tissues. Although past research has implicated cellular heterogeneity in chondrocyte populations, advances over the past decade in single-cell transcriptomics now enable a more granular, functionally annotated classification of chondrocyte subtypes. These analyses provide crucial insights into the role of these subtypes in cartilage formation, maintenance and disease progression. Chondrocyte populations are implicated in tissue homeostasis, pathogenesis and responses to external stimuli, including pro-inflammatory mediators and novel therapeutic agents. This knowledge opens pathways for developing targeted treatments for diseases such as osteoarthritis and intervertebral disc disease. Insights into the molecular signatures of disease-critical chondrocyte populations provide a foundation for biomarker discovery and therapeutic targeting, and there are exciting opportunities for leveraging these findings to progress regenerative therapies. Spatial and temporal profiling of cellular markers, behaviour and metabolic activity will enhance understanding of disease pathogenesis and chondrosenescence and could possibly enable early intervention for osteoarthritis, thereby preventing irreversible joint damage. Future research must integrate advanced single-cell techniques with computational modelling to unravel the dynamic interplay of chondrocyte populations. These efforts could transform precision medicine in rheumatology, addressing the unmet clinical needs in cartilage-related diseases. This Review provides an update on chondrocyte heterogeneity in cartilaginous tissues in health, disease and senescence focusing on insights gained from single-cell analyses. The authors highlight how single-cell multi-omics techniques could reveal new biomarkers and therapeutic targets for conditions such as osteoarthritis and intervertebral disc degeneration.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 8","pages":"465-477"},"PeriodicalIF":32.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594670","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}

{"title":"Tissue-resident memory CD8+ T cells on the skin–joint route","authors":"Maria Papatriantafyllou","doi":"10.1038/s41584-025-01284-z","DOIUrl":"10.1038/s41584-025-01284-z","url":null,"abstract":"Skin- and joint-resident CD8+ T cells that share clonality also share phenotypic similarities in psoriatic arthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 8","pages":"441-441"},"PeriodicalIF":32.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586417","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}

{"title":"Nerandomilast slows progression of pulmonary fibrosis","authors":"Maria Papatriantafyllou","doi":"10.1038/s41584-025-01285-y","DOIUrl":"10.1038/s41584-025-01285-y","url":null,"abstract":"The anti-fibrotic and anti-inflammatory agent nerandomilast has shown promise for the treatment of both idiopathic and progressive pulmonary fibrosis in phase III trials.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 8","pages":"441-441"},"PeriodicalIF":32.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586418","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}

{"title":"Synovial fibroblast-mediated neovascularization in RA","authors":"Holly Webster","doi":"10.1038/s41584-025-01283-0","DOIUrl":"10.1038/s41584-025-01283-0","url":null,"abstract":"A study provides insights into the factors that regulate synovial fibroblast interactions with endothelial cells in RA and subsequent pathogenic neovascularization.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 8","pages":"442-442"},"PeriodicalIF":32.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586416","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}

{"title":"Synovial fluid as a complex molecular pool contributing to knee osteoarthritis","authors":"Hayley Peters, Jason S. Rockel, Christopher B. Little, Mohit Kapoor","doi":"10.1038/s41584-025-01271-4","DOIUrl":"10.1038/s41584-025-01271-4","url":null,"abstract":"The main homeostatic function of the synovial fluid is joint lubrication. However, during knee osteoarthritis (KOA), synovial fluid becomes modified with drivers of disease that contribute to symptoms (pain) and joint-related pathology. Acting as a sink of factors from both systemic circulation and local tissues, including articular cartilage, subchondral bone, synovium, and the infrapatellar fat pad, the synovial fluid enables bidirectional communication promoting KOA pathogenesis. Synovial fluid constituents might also be detected in circulation, functioning not only as accessible biomarkers but also as potential mediators of KOA-driven systemic effects. Factors deposited in synovial fluid have the ability to affect nervous system activity, acting at the neuronal projections that are integrated into joint tissues from dorsal root ganglia. Non-coding RNAs (microRNAs, long non-coding RNAs, circular RNAs), metabolites, cytokines and other secreted proteins of the synovial fluid in KOA have emerged as biomarkers of disease progression, therapeutic efficacy, and pain. These molecules might also function as molecular mediators of KOA, supporting them as candidates for therapeutic intervention. This review consolidates literature published primarily within the past 4 years, focussing on factors identified within synovial fluid as biomarkers and molecular mediators of KOA symptoms and pathology. Emerging therapeutic modalities to target synovial fluid molecular mediators are also discussed. The synovial fluid lubricates joints while also collecting molecular mediators from surrounding tissues. This Review highlights how molecular analyses of the synovial fluid might provide information on the progression of knee osteoarthritis and treatment efficacy, and identify potential therapeutic strategies targeting synovial fluid mediators in knee osteoarthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 8","pages":"447-464"},"PeriodicalIF":32.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568815","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}

{"title":"Platelets as drivers of immunothrombosis in rheumatic diseases","authors":"Norma Maugeri, Angelo A. Manfredi","doi":"10.1038/s41584-025-01276-z","DOIUrl":"10.1038/s41584-025-01276-z","url":null,"abstract":"Platelets are central players in inflammatory and thrombotic responses that drive the onset and progression of rheumatic diseases. In particular, they regulate immunothrombosis, a defence mechanism in which the immune and blood-clotting systems cooperate to contain infections or vascular damage. Although immunothrombosis can help to preserve blood-vessel integrity and promote healing, it becomes harmful when exaggerated or chronic. In rheumatic diseases, such as systemic lupus erythematosus, systemic sclerosis and antiphospholipid syndrome, immunothrombosis contributes to persistent inflammation, abnormal blood-clot formation and long-term damage to the small blood vessels. It has also been implicated in maintaining autoimmune responses to autoantigens released by neutrophils. Platelets are among the first responders to vascular injury and influence the activity of immune cells, particularly neutrophils, by promoting the formation of neutrophil extracellular traps. Platelets express proteins such as P-selectin and the damage-associated molecule high-mobility group box 1 (HMGB1), which have distinct and non-redundant roles, both via direct interactions locally at sites of vascular damage and systemically via the release of extracellular vesicles. Understanding how platelets contribute to vascular inflammation and clotting in autoimmune settings elucidates disease mechanisms and might lead to the identification of new therapeutic targets. This Review provides an overview of how platelets promote immunothrombosis in rheumatic disease. The authors discuss the different ways in which platelets and immunothrombosis can be targeted for therapeutic intervention.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 8","pages":"478-493"},"PeriodicalIF":32.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568816","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}

{"title":"CAR T cell therapy for children with rheumatic disease: the time is now","authors":"Holly Wobma, Stacy P. Ardoin, Challice L. Bonifant, Jennifer C. Cooper, Hanna Kim, Rebecca E. Sadun, Laura Lewandowski, Michael Keller, Robert A. Colbert, Cuoghi Edens, Kimberly DeQuattro, Kyla Driest, Julia Shalen, Ivana Stojkic, Andrea Knight, Colleen Annesley, Kathryn S. Torok, Caitlin W. Elgarten, Toshihiro Onishi, Shaun W. Jackson, Susan Prockop, Nirali N. Shah, Kaveh Ardalan, Margaret Lamb, on behalf of the Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group*","doi":"10.1038/s41584-025-01272-3","DOIUrl":"10.1038/s41584-025-01272-3","url":null,"abstract":"Initial success with B cell-targeted chimeric antigen receptor (CAR) T cells for the treatment of systemic lupus erythematosus and other rheumatic diseases has generated enthusiasm for the broad application of this technology outside of the field of oncology. Paediatric patients with severe rheumatic diseases require lifelong therapy with a substantial toxicity burden and a high cost of care. Paradigm-shifting treatments, including CAR T cells, are desperately needed. Although CAR T cell therapy shows promise for paediatric rheumatic diseases, there are unique aspects of care compared with adults, which require careful consideration and expertise. In response, we established the Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group, comprising international experts in the fields of paediatric rheumatology, oncology and cellular therapy, immunology and nephrology, to address the challenges of introducing cell therapies to patients with paediatric-onset autoimmune diseases. Given the possible benefits, we advocate for the study of CAR T cells in paediatric patients with rheumatic diseases who carry a lifelong risk of morbidity and mortality from chronic illness and medication toxicity. As this patient population is relatively small, consensus around definitions of success, robust study of predictors of response and uniform assessment and reporting of toxicities are critical to advancing the field. In this Perspective, the authors and the members of the Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group discuss specific considerations for the use of chimeric antigen receptor (CAR) T cell therapies in paediatric patients with rheumatic diseases.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 8","pages":"494-506"},"PeriodicalIF":32.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547240","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}

{"title":"Location-specific treatment of chronic inflammatory joint disease","authors":"Adrian Ciurea, Caroline Ospelt","doi":"10.1038/s41584-025-01278-x","DOIUrl":"10.1038/s41584-025-01278-x","url":null,"abstract":"Over the past decades, considerable progress has been made in the pharmacological treatment of immune-mediated joint diseases such as rheumatoid arthritis and psoriatic arthritis; however, treatment-resistant arthritis remains a major clinical challenge. To tackle insufficient treatment outcomes, further research into the underlying mechanisms and patterns of non-responsiveness is needed.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 9","pages":"507-508"},"PeriodicalIF":32.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479043","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}

{"title":"Immunometabolism in systemic lupus erythematosus","authors":"Eduardo Patiño-Martinez, Mariana J. Kaplan","doi":"10.1038/s41584-025-01267-0","DOIUrl":"10.1038/s41584-025-01267-0","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by chronic inflammation, tissue damage, accelerated cardiovascular disease and the synthesis of autoantibodies that target nucleic acids and nuclear protein complexes. Emerging evidence underscores the key role of immune metabolic dysregulation in SLE, revealing how metabolic reprogramming during immune cell activation influences disease development and progression. Alterations in key metabolic pathways such as glycolysis and oxidative phosphorylation profoundly affect the activation, differentiation and function of B and T cells, monocytes, neutrophils and other immune cells, driving inflammation and tissue injury. This Review synthesizes current findings on immune cell metabolism in animal models of lupus and in patients with SLE, highlighting the interplay of metabolic disturbances, mitochondrial dysfunction and disease pathogenesis. Furthermore, it explores the potential of targeting metabolic pathways as therapeutic strategies to mitigate organ damage and improve outcomes in SLE. Systemic lupus erythematosus is characterized by altered metabolic profiles and changes in immune cell metabolism. The authors review these changes and discuss how interventions that target metabolic processes might provide treatment options in systemic lupus erythematosus.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 7","pages":"377-395"},"PeriodicalIF":32.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296012","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}

{"title":"2023 International Rome consensus for the nomenclature of Sjögren disease","authors":"Manuel Ramos-Casals, Alan N. Baer, María del Pilar Brito-Zerón, Katherine M. Hammitt, Coralie Bouillot, Soledad Retamozo, Alison Mackey, David Yarowsky, Breck Turner, Jaime Blanck, Benjamin A. Fisher, Esen K. Akpek, Chiara Baldini, Hendrika Bootsma, Simon J. Bowman, Thomas Dörner, Leslie Laing, Scott M. Lieberman, Xavier Mariette, Stephen C. Pflugfelder, Vidya Sankar, Antoni Sisó-Almirall, Athanasios G. Tzioufas, Juan-Manuel Anaya, Berkan Armağan, Michele Bombardieri, Steven Carsons, Salvatore de Vita, Robert I. Fox, Roberto Gerli, Roberto Giacomelli, Jacques Eric Gottenberg, Gabriela Hernández-Molina, Roland Jonsson, Aike Kruize, Seung-Ki Kwok, Xiaomei Li, Sara S. McCoy, Wan-Fai Ng, Peter Olsson, Maureen Rischmueller, Alain Saraux, R. Hal Scofield, Valéria Valim, Claudio Vitali, Frederick Vivino, Marie Wahren-Herlenius, Haralampos M. Moutsopoulos, on behalf of the International Task Force on Nomenclature of Sjögren Disease","doi":"10.1038/s41584-025-01268-z","DOIUrl":"10.1038/s41584-025-01268-z","url":null,"abstract":"Nomenclature for the disease widely known as Sjögren syndrome has proven unsatisfactory. Patients have perceived ‘syndrome’ as indicative of a vague collection of symptoms, prompting the Sjögren’s Foundation to abandon the term. Furthermore, the traditional distinction between ‘primary’ and ‘secondary’ forms fails to account for the complex interplay between overlapping autoimmune diseases. Following a bibliometric analysis, systematic literature review and a Delphi consensus process with equal involvement of professional and patient representatives, five recommendations are now issued. First, the term ‘Sjögren disease’ should replace ‘Sjögren syndrome’. Second, the acronym ‘SjD’ should be used as an abbreviation for ‘Sjögren disease’. Third, the descriptor ‘associated’ should be used in lieu of ‘secondary’ for Sjögren disease occurring in association with a second systemic autoimmune disease for which classification criteria are fulfilled. Fourth, Sjögren disease is the preferred terminology in common parlance and in clinical diagnosis, without differentiation as to primary and associated forms. Fifth, the differentiation between primary and associated Sjögren is recommended for scientific studies to define a homogeneous population. In conclusion, the consensus endorses ‘Sjögren disease’ as the official nomenclature to acknowledge the distinct pathogenesis of this disorder and to improve clarity in both clinical practice and research. In this Consensus Statement, an international group of experts and patient representatives validates and endorses the transition from the term ‘Sjögren syndrome’ to ‘Sjögren disease’, and issue several additional recommendations regarding the nomenclature of this disorder.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 7","pages":"426-437"},"PeriodicalIF":32.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41584-025-01268-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252759","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}