{"title":"Rebalancing Inflammation in Arthritis: PEPITEM as a Restorer of Immune Regulation","authors":"Mattias N.D Svensson, Nunzio Bottini","doi":"10.1002/art.70084","DOIUrl":"https://doi.org/10.1002/art.70084","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"24 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122073","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}
Yiwei Shen, Jingyi Peng, Dai Dai, Min Dai, Ting Li, Sheng Chen, Shuang Ye, Nan Shen, Huihua Ding
{"title":"Reply to the Letter to the Editor.","authors":"Yiwei Shen, Jingyi Peng, Dai Dai, Min Dai, Ting Li, Sheng Chen, Shuang Ye, Nan Shen, Huihua Ding","doi":"10.1002/art.70080","DOIUrl":"https://doi.org/10.1002/art.70080","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117207","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":"When blood proteins reveal what transcripts miss: immune cell priming and the road to prognostic biomarkers in lupus","authors":"Ioannis Parodis","doi":"10.1002/art.70065","DOIUrl":"https://doi.org/10.1002/art.70065","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"39 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122074","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}
Karen H Costenbader, Daniel H Solomon, S Louis Bridges
{"title":"Big Data May Have Big Pitfalls: Ensuring Rigor in Rheumatic Disease Epidemiology.","authors":"Karen H Costenbader, Daniel H Solomon, S Louis Bridges","doi":"10.1002/art.70067","DOIUrl":"https://doi.org/10.1002/art.70067","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117194","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}
Fenli Shao, Shuqiong Zhang, Zhigui Wu, Tonghao Zhang, Hui Liu, Qiang Xu, Dijun Chen, Haiguo Yu, Zhidan Fan, Yang Sun
Objective: Ankylosing spondylitis (AS) and enthesitis-related arthritis (ERA) are autoimmune bone diseases characterized by prominent heterotopic ossification and are both poor prognosis. The pathological mechanisms of these diseases remain poorly understood.
Methods: After single-cell RNA-seq and TCR profiling, we used flow cytometry and multiplex immunofluorescence to quantify and map specific immune cell subsets within lesions of early rheumatoid arthritis and ankylosing spondylitis (AS), analyzing a total of 33 patient specimens. Furthermore, we identified a peptide from versican, a chondroitin sulfate proteoglycan of ligament, to establish AS mouse model. In the novel model, immune-cell quantification, spatial mapping, and targeted therapies were applied to elucidate the pathogenic roles of key cellular subpopulations.
Results: Conventional type 1 dendritic cells (cDC1s) were enriched in the joints of patients with ERA and exhibited a high level of MHC I antigen presentation, which robustly interact with CD8+ T cells. Moreover, cDC1s, harboring the molecular of MHC I antigen presentation, were detected in spinal ligament tissue of patients with AS. In mice, versican-derived peptide combined with type II collagen stably and efficiently elicits a model exhibiting hallmark enthesitis and heterotopic ossification. In this model, cDC1s and IL-17A+CD8+ T cells were highly enriched in the ligamentous synovial tissues. Blocking the recruitment of cDC1s through XCL1 neutralizing antibody alleviates arthritis symptoms in vivo.
Conclusion: Thus, cDC1s promote autoimmune reactions and osteoarticular lesions through IL-17A+CD8+ T cells. Targeting cDC1 represents a novel therapeutic target for bone remodeling arthritis.
{"title":"XCR1<sup>+</sup> Conventional type 1 dendritic cells exacerbate the inflammation in osteogenic arthritis through IL-17A<sup>+</sup>CD8<sup>+</sup> T cells.","authors":"Fenli Shao, Shuqiong Zhang, Zhigui Wu, Tonghao Zhang, Hui Liu, Qiang Xu, Dijun Chen, Haiguo Yu, Zhidan Fan, Yang Sun","doi":"10.1002/art.70069","DOIUrl":"https://doi.org/10.1002/art.70069","url":null,"abstract":"<p><strong>Objective: </strong>Ankylosing spondylitis (AS) and enthesitis-related arthritis (ERA) are autoimmune bone diseases characterized by prominent heterotopic ossification and are both poor prognosis. The pathological mechanisms of these diseases remain poorly understood.</p><p><strong>Methods: </strong>After single-cell RNA-seq and TCR profiling, we used flow cytometry and multiplex immunofluorescence to quantify and map specific immune cell subsets within lesions of early rheumatoid arthritis and ankylosing spondylitis (AS), analyzing a total of 33 patient specimens. Furthermore, we identified a peptide from versican, a chondroitin sulfate proteoglycan of ligament, to establish AS mouse model. In the novel model, immune-cell quantification, spatial mapping, and targeted therapies were applied to elucidate the pathogenic roles of key cellular subpopulations.</p><p><strong>Results: </strong>Conventional type 1 dendritic cells (cDC1s) were enriched in the joints of patients with ERA and exhibited a high level of MHC I antigen presentation, which robustly interact with CD8<sup>+</sup> T cells. Moreover, cDC1s, harboring the molecular of MHC I antigen presentation, were detected in spinal ligament tissue of patients with AS. In mice, versican-derived peptide combined with type II collagen stably and efficiently elicits a model exhibiting hallmark enthesitis and heterotopic ossification. In this model, cDC1s and IL-17A<sup>+</sup>CD8<sup>+</sup> T cells were highly enriched in the ligamentous synovial tissues. Blocking the recruitment of cDC1s through XCL1 neutralizing antibody alleviates arthritis symptoms in vivo.</p><p><strong>Conclusion: </strong>Thus, cDC1s promote autoimmune reactions and osteoarticular lesions through IL-17A<sup>+</sup>CD8<sup>+</sup> T cells. Targeting cDC1 represents a novel therapeutic target for bone remodeling arthritis.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117285","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}
Kensuke Suga, Amara Seng, Changfu Yao, Tanyalak Parimon, Anvita Singaraju, Edo Israely, Beulah Esther Rani Samuel, Youn Jung Choi, Justyna Fert-Bober, Barry R Stripp, Paul J Wolters, Jon T Giles, Peter Chen, Nunzio Bottini
Objective: Little is known about the pathogenesis of rheumatoid arthritis-related interstitial lung disease (RA-ILD). This study aimed to clarify the cellular and transcriptomic landscape of epithelial and immune cells in RA-ILD.
Methods: We performed single-cell RNA sequencing on fluorescence-activated cell sorted epithelial cells and immune cells from lung explants of four controls, three non-RA connective tissue disease (CTD)-ILD patients, and five RA-ILD patients. For T cell subclusters, we performed an integrative analysis with publicly available synovial T cell data. We performed immunofluorescence staining on lung sections from four controls, nine RA-ILD patients, eight non-RA CTD-ILD patients, and six idiopathic pulmonary fibrosis (IPF) patients.
Results: We profiled 184,814 cells in total and identified 18 distinct cell clusters. We found fewer alveolar type 2 cells with reciprocally higher frequencies of other epithelial cell types (basal cells and ciliated cells) and fewer FCN1+ CD14+ monocytes in RA-ILD lungs. In T cell subset analysis, peripheral helper T cells (Tph) were exclusively observed in RA-ILD lungs. Compared with synovial Tph cells, lung Tph cells had elevated expression profiles of activation and lower cytotoxic and exhausted signatures. From gene ontology analysis, genes associated with the small GTPase-mediated signal transduction were enriched in lung Tph cells. On confirmatory immunofluorescence staining, Tph cells were specifically present in RA-ILD lungs.
Conclusion: We report a detailed transcriptomic analysis of the epithelial and immune cells in RA-ILD lungs and include a cross-tissue comparison that demonstrates organ-specific variations in the characteristics of Tph cells.
{"title":"Single-cell analysis reveals peripheral helper T cells in rheumatoid arthritis-related interstitial lung disease.","authors":"Kensuke Suga, Amara Seng, Changfu Yao, Tanyalak Parimon, Anvita Singaraju, Edo Israely, Beulah Esther Rani Samuel, Youn Jung Choi, Justyna Fert-Bober, Barry R Stripp, Paul J Wolters, Jon T Giles, Peter Chen, Nunzio Bottini","doi":"10.1002/art.70066","DOIUrl":"https://doi.org/10.1002/art.70066","url":null,"abstract":"<p><strong>Objective: </strong>Little is known about the pathogenesis of rheumatoid arthritis-related interstitial lung disease (RA-ILD). This study aimed to clarify the cellular and transcriptomic landscape of epithelial and immune cells in RA-ILD.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing on fluorescence-activated cell sorted epithelial cells and immune cells from lung explants of four controls, three non-RA connective tissue disease (CTD)-ILD patients, and five RA-ILD patients. For T cell subclusters, we performed an integrative analysis with publicly available synovial T cell data. We performed immunofluorescence staining on lung sections from four controls, nine RA-ILD patients, eight non-RA CTD-ILD patients, and six idiopathic pulmonary fibrosis (IPF) patients.</p><p><strong>Results: </strong>We profiled 184,814 cells in total and identified 18 distinct cell clusters. We found fewer alveolar type 2 cells with reciprocally higher frequencies of other epithelial cell types (basal cells and ciliated cells) and fewer FCN1<sup>+</sup> CD14<sup>+</sup> monocytes in RA-ILD lungs. In T cell subset analysis, peripheral helper T cells (Tph) were exclusively observed in RA-ILD lungs. Compared with synovial Tph cells, lung Tph cells had elevated expression profiles of activation and lower cytotoxic and exhausted signatures. From gene ontology analysis, genes associated with the small GTPase-mediated signal transduction were enriched in lung Tph cells. On confirmatory immunofluorescence staining, Tph cells were specifically present in RA-ILD lungs.</p><p><strong>Conclusion: </strong>We report a detailed transcriptomic analysis of the epithelial and immune cells in RA-ILD lungs and include a cross-tissue comparison that demonstrates organ-specific variations in the characteristics of Tph cells.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103218","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":"Where You Live Shouldn't Dictate Your Care: Multilateral Strategies Are Needed for National and Regional Equity in Psoriatic Arthritis Treatment.","authors":"Jihwan Hwang,Ashira Blazer,Irene Blanco","doi":"10.1002/art.70063","DOIUrl":"https://doi.org/10.1002/art.70063","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"3 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072935","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}