Pub Date : 2024-08-01DOI: 10.1038/s41584-024-01144-2
Luis M. Franco
Glucocorticoids are important anti-inflammatory and immunosuppressive drugs and potent regulators of metabolism. However, their immune and metabolic effects have been treated as separate entities. New research is shedding light onto the intersection between the immunoregulatory and metabolic effects of glucocorticoids.
{"title":"Shedding light onto the immunometabolic effects of glucocorticoids","authors":"Luis M. Franco","doi":"10.1038/s41584-024-01144-2","DOIUrl":"10.1038/s41584-024-01144-2","url":null,"abstract":"Glucocorticoids are important anti-inflammatory and immunosuppressive drugs and potent regulators of metabolism. However, their immune and metabolic effects have been treated as separate entities. New research is shedding light onto the intersection between the immunoregulatory and metabolic effects of glucocorticoids.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 9","pages":"529-530"},"PeriodicalIF":29.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875305","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 : 2024-07-29DOI: 10.1038/s41584-024-01148-y
Maria Papatriantafyllou
Early data indicate that allogeneic CAR T cell therapy targeting B cells is a scalable and safe therapeutic strategy in refractory autoimmunity.
早期数据表明，针对 B 细胞的异体 CAR T 细胞疗法是治疗难治性自身免疫病的一种可扩展且安全的治疗策略。
{"title":"Off-the-shelf CAR T cells for refractory autoimmunity","authors":"Maria Papatriantafyllou","doi":"10.1038/s41584-024-01148-y","DOIUrl":"10.1038/s41584-024-01148-y","url":null,"abstract":"Early data indicate that allogeneic CAR T cell therapy targeting B cells is a scalable and safe therapeutic strategy in refractory autoimmunity.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 9","pages":"527-527"},"PeriodicalIF":29.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791010","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 : 2024-07-26DOI: 10.1038/s41584-024-01147-z
Holly Webster
Two studies have identified variants of UNC93B1 that are associated with enhanced TLR7 and TLR8 activity and the development of systemic lupus erythematosus.
{"title":"UNC93B1 variants promote SLE via TLR activation","authors":"Holly Webster","doi":"10.1038/s41584-024-01147-z","DOIUrl":"10.1038/s41584-024-01147-z","url":null,"abstract":"Two studies have identified variants of UNC93B1 that are associated with enhanced TLR7 and TLR8 activity and the development of systemic lupus erythematosus.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 9","pages":"528-528"},"PeriodicalIF":29.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766737","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 : 2024-07-16DOI: 10.1038/s41584-024-01130-8
Michael Z. Miao, Janice S. Lee, Kenneth M. Yamada, Richard F. Loeser
Integrins are key regulators of cell–matrix interactions during joint development and joint tissue homeostasis, as well as in the development of osteoarthritis (OA). The signalling cascades initiated by the interactions of integrins with a complex network of extracellular matrix (ECM) components and intracellular adaptor proteins orchestrate cellular responses necessary for maintaining joint tissue integrity. Dysregulated integrin signalling, triggered by matrix degradation products such as matrikines, disrupts this delicate balance, tipping the scales towards an environment conducive to OA pathogenesis. The interplay between integrin signalling and growth factor pathways further underscores the multifaceted nature of OA. Moreover, emerging insights into the role of endocytic trafficking in regulating integrin signalling add a new layer of complexity to the understanding of OA development. To harness the therapeutic potential of targeting integrins for mitigation of OA, comprehensive understanding of their molecular mechanisms across joint tissues is imperative. Ultimately, deciphering the complexities of integrin signalling will advance the ability to treat OA and alleviate its global burden. Integrins are involved in joint tissue development and homeostasis, and perturbations in the availability of integrin ligands or in downstream integrin signalling are linked to the pathogenesis of osteoarthritis (OA). This Review discusses current evidence and future perspectives for therapeutically targeting integrins in OA.
整合素是关节发育、关节组织稳态以及骨关节炎（OA）发生过程中细胞与基质相互作用的关键调节因子。整合素与细胞外基质（ECM）成分和细胞内适配蛋白组成的复杂网络相互作用所启动的信号级联协调了维持关节组织完整性所必需的细胞反应。由基质降解产物（如 matrikines）引发的整合素信号失调会破坏这种微妙的平衡，使天平向有利于 OA 发病的环境倾斜。整合素信号和生长因子通路之间的相互作用进一步凸显了 OA 的多面性。此外，关于内细胞转运在调节整合素信号传导中的作用的新见解为人们了解 OA 的发展增加了一层新的复杂性。要利用靶向整合素的治疗潜力缓解 OA，就必须全面了解整合素在关节组织中的分子机制。最终，破译整合素信号的复杂性将提高治疗 OA 的能力并减轻其全球负担。
{"title":"Integrin signalling in joint development, homeostasis and osteoarthritis","authors":"Michael Z. Miao, Janice S. Lee, Kenneth M. Yamada, Richard F. Loeser","doi":"10.1038/s41584-024-01130-8","DOIUrl":"10.1038/s41584-024-01130-8","url":null,"abstract":"Integrins are key regulators of cell–matrix interactions during joint development and joint tissue homeostasis, as well as in the development of osteoarthritis (OA). The signalling cascades initiated by the interactions of integrins with a complex network of extracellular matrix (ECM) components and intracellular adaptor proteins orchestrate cellular responses necessary for maintaining joint tissue integrity. Dysregulated integrin signalling, triggered by matrix degradation products such as matrikines, disrupts this delicate balance, tipping the scales towards an environment conducive to OA pathogenesis. The interplay between integrin signalling and growth factor pathways further underscores the multifaceted nature of OA. Moreover, emerging insights into the role of endocytic trafficking in regulating integrin signalling add a new layer of complexity to the understanding of OA development. To harness the therapeutic potential of targeting integrins for mitigation of OA, comprehensive understanding of their molecular mechanisms across joint tissues is imperative. Ultimately, deciphering the complexities of integrin signalling will advance the ability to treat OA and alleviate its global burden. Integrins are involved in joint tissue development and homeostasis, and perturbations in the availability of integrin ligands or in downstream integrin signalling are linked to the pathogenesis of osteoarthritis (OA). This Review discusses current evidence and future perspectives for therapeutically targeting integrins in OA.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 8","pages":"492-509"},"PeriodicalIF":29.4,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625031","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 : 2024-07-11DOI: 10.1038/s41584-024-01137-1
Megan P. Leask, Tania O. Crișan, Aichang Ji, Hirotaka Matsuo, Anna Köttgen, Tony R. Merriman
The pathogenesis of gout involves a series of steps beginning with hyperuricaemia, followed by the deposition of monosodium urate crystal in articular structures and culminating in an innate immune response, mediated by the NLRP3 inflammasome, to the deposited crystals. Large genome-wide association studies (GWAS) of serum urate levels initially identified the genetic variants with the strongest effects, mapping mainly to genes that encode urate transporters in the kidney and gut. Other GWAS highlighted the importance of uncommon genetic variants. More recently, genetic and epigenetic genome-wide studies have revealed new pathways in the inflammatory process of gout, including genetic associations with epigenomic modifiers. Epigenome-wide association studies are also implicating epigenomic remodelling in gout, which perhaps regulates the responsiveness of the innate immune system to monosodium urate crystals. Notably, genes implicated in gout GWAS do not include those encoding components of the NLRP3 inflammasome itself, but instead include genes encoding molecules involved in its regulation. Knowledge of the molecular mechanisms underlying gout has advanced through the translation of genetic associations into specific molecular mechanisms. Notable examples include ABCG2, HNF4A, PDZK1, MAF and IL37. Current genetic studies are dominated by participants of European ancestry; however, studies focusing on other population groups are discovering informative population-specific variants associated with gout. Genetic, epigenetic and transcriptomic studies in hyperuricaemia and gout have, in the past 6 years, provided important insights into the underlying molecular mechanisms, revealing new inflammatory pathways and epigenetic factors and expanding research beyond European populations.
{"title":"The pathogenesis of gout: molecular insights from genetic, epigenomic and transcriptomic studies","authors":"Megan P. Leask, Tania O. Crișan, Aichang Ji, Hirotaka Matsuo, Anna Köttgen, Tony R. Merriman","doi":"10.1038/s41584-024-01137-1","DOIUrl":"10.1038/s41584-024-01137-1","url":null,"abstract":"The pathogenesis of gout involves a series of steps beginning with hyperuricaemia, followed by the deposition of monosodium urate crystal in articular structures and culminating in an innate immune response, mediated by the NLRP3 inflammasome, to the deposited crystals. Large genome-wide association studies (GWAS) of serum urate levels initially identified the genetic variants with the strongest effects, mapping mainly to genes that encode urate transporters in the kidney and gut. Other GWAS highlighted the importance of uncommon genetic variants. More recently, genetic and epigenetic genome-wide studies have revealed new pathways in the inflammatory process of gout, including genetic associations with epigenomic modifiers. Epigenome-wide association studies are also implicating epigenomic remodelling in gout, which perhaps regulates the responsiveness of the innate immune system to monosodium urate crystals. Notably, genes implicated in gout GWAS do not include those encoding components of the NLRP3 inflammasome itself, but instead include genes encoding molecules involved in its regulation. Knowledge of the molecular mechanisms underlying gout has advanced through the translation of genetic associations into specific molecular mechanisms. Notable examples include ABCG2, HNF4A, PDZK1, MAF and IL37. Current genetic studies are dominated by participants of European ancestry; however, studies focusing on other population groups are discovering informative population-specific variants associated with gout. Genetic, epigenetic and transcriptomic studies in hyperuricaemia and gout have, in the past 6 years, provided important insights into the underlying molecular mechanisms, revealing new inflammatory pathways and epigenetic factors and expanding research beyond European populations.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 8","pages":"510-523"},"PeriodicalIF":29.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590798","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 : 2024-07-10DOI: 10.1038/s41584-024-01142-4
Sarah Onuora
Treatment with the endogenous metabolite itaconate induced phenotypic and metabolic changes in fibroblast-like synoviocytes and reduced the severity of arthritis in an animal model.
{"title":"Itaconate targets fibroblast-like synoviocytes in RA","authors":"Sarah Onuora","doi":"10.1038/s41584-024-01142-4","DOIUrl":"10.1038/s41584-024-01142-4","url":null,"abstract":"Treatment with the endogenous metabolite itaconate induced phenotypic and metabolic changes in fibroblast-like synoviocytes and reduced the severity of arthritis in an animal model.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 8","pages":"456-456"},"PeriodicalIF":29.4,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576282","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 : 2024-07-09DOI: 10.1038/s41584-024-01135-3
Chiara Baldini, Giovanni Fulvio, Gaetano La Rocca, Francesco Ferro
Sjögren syndrome or Sjögren disease is a chronic form of autoimmune epithelitis characterized by lymphocytic infiltration of the exocrine glands, particularly the salivary and lacrimal glands, leading to progressive glandular dysfunction and subsequent xerostomia and xerophthalmia. Other common manifestations include pain and fatigue, various systemic manifestations and non-Hodgkin’s lymphoma. Sjögren syndrome is therefore a complex and disabling disease associated with a reduced quality of life and with considerable long-term damage. Most of the available treatments are merely symptomatic with limited efficacy in both preventing glandular damage and suppressing systemic disease activity. In the past 10 years, great progress has been made in understanding the pathophysiology of Sjögren syndrome, opening new avenues towards a more targeted and individualized therapeutic approach to the disease. Indeed, several randomized controlled trials have just been completed or are poised to commence evaluating the effectiveness of novel drugs targeting both innate and adaptive immune pathways, including pro-inflammatory cytokines, the type I interferon system, B cell activation, B cell and T cell co-stimulation pathway, and ectopic germinal centre formation. Novel clinical trials are also ongoing exploring various targeted approaches (that is, IgG recycling inhibition, nuclease therapy and CAR-T cell therapy) for Sjögren syndrome. Sjögren syndrome is a chronic autoimmune disease affecting exocrine glands, causing dryness and systemic symptoms. Treatment has been primarily symptomatic, but advances in our understanding of its pathophysiology offer promise for targeted therapies, aiming for personalized care and improved outcomes.
{"title":"Update on the pathophysiology and treatment of primary Sjögren syndrome","authors":"Chiara Baldini, Giovanni Fulvio, Gaetano La Rocca, Francesco Ferro","doi":"10.1038/s41584-024-01135-3","DOIUrl":"10.1038/s41584-024-01135-3","url":null,"abstract":"Sjögren syndrome or Sjögren disease is a chronic form of autoimmune epithelitis characterized by lymphocytic infiltration of the exocrine glands, particularly the salivary and lacrimal glands, leading to progressive glandular dysfunction and subsequent xerostomia and xerophthalmia. Other common manifestations include pain and fatigue, various systemic manifestations and non-Hodgkin’s lymphoma. Sjögren syndrome is therefore a complex and disabling disease associated with a reduced quality of life and with considerable long-term damage. Most of the available treatments are merely symptomatic with limited efficacy in both preventing glandular damage and suppressing systemic disease activity. In the past 10 years, great progress has been made in understanding the pathophysiology of Sjögren syndrome, opening new avenues towards a more targeted and individualized therapeutic approach to the disease. Indeed, several randomized controlled trials have just been completed or are poised to commence evaluating the effectiveness of novel drugs targeting both innate and adaptive immune pathways, including pro-inflammatory cytokines, the type I interferon system, B cell activation, B cell and T cell co-stimulation pathway, and ectopic germinal centre formation. Novel clinical trials are also ongoing exploring various targeted approaches (that is, IgG recycling inhibition, nuclease therapy and CAR-T cell therapy) for Sjögren syndrome. Sjögren syndrome is a chronic autoimmune disease affecting exocrine glands, causing dryness and systemic symptoms. Treatment has been primarily symptomatic, but advances in our understanding of its pathophysiology offer promise for targeted therapies, aiming for personalized care and improved outcomes.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 8","pages":"473-491"},"PeriodicalIF":29.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563769","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 : 2024-07-08DOI: 10.1038/s41584-024-01141-5
Jessica McHugh
New findings identify HSP60 and other synovial stromal-derived autoantigens as targets for pathogenic autoantibodies, exacerbating arthritis and serving as potential biomarkers.
{"title":"Pathogenic antibodies target stromal antigens in RA","authors":"Jessica McHugh","doi":"10.1038/s41584-024-01141-5","DOIUrl":"10.1038/s41584-024-01141-5","url":null,"abstract":"New findings identify HSP60 and other synovial stromal-derived autoantigens as targets for pathogenic autoantibodies, exacerbating arthritis and serving as potential biomarkers.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 9","pages":"527-527"},"PeriodicalIF":29.4,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556764","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 : 2024-07-08DOI: 10.1038/s41584-024-01140-6
Jessica McHugh
Type 2 innate lymphoid cells protect against kidney inflammation in lupus nephritis, and enhancing their adhesion via integrin α4β7 upregulation, particularly through IL-33 treatment, could be a promising therapeutic approach.
{"title":"Integrin-mediated ILC2 adhesion protects against lupus nephritis","authors":"Jessica McHugh","doi":"10.1038/s41584-024-01140-6","DOIUrl":"10.1038/s41584-024-01140-6","url":null,"abstract":"Type 2 innate lymphoid cells protect against kidney inflammation in lupus nephritis, and enhancing their adhesion via integrin α4β7 upregulation, particularly through IL-33 treatment, could be a promising therapeutic approach.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 8","pages":"455-455"},"PeriodicalIF":29.4,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556983","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 : 2024-07-05DOI: 10.1038/s41584-024-01138-0
Maria Papatriantafyllou
FNIP1- and TFEB-dependent secretion of IGF2 by dystrophic muscles contributes to muscle–bone crosstalk.
萎缩性肌肉分泌 IGF2 依赖于 FNIP1 和 TFEB，这有助于肌肉与骨骼之间的串联。
{"title":"How muscle influences bone health","authors":"Maria Papatriantafyllou","doi":"10.1038/s41584-024-01138-0","DOIUrl":"10.1038/s41584-024-01138-0","url":null,"abstract":"FNIP1- and TFEB-dependent secretion of IGF2 by dystrophic muscles contributes to muscle–bone crosstalk.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 8","pages":"456-456"},"PeriodicalIF":29.4,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538192","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}
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