25rhk02910.3205/25rhk029urn:nbn:de:0183-25rhk0293Meeting AbstractSingle-cell profiling reveals functional remodeling of CD8+ recent thymic emigrants in rheumatoid arthritisSouto-CarneiroSouto-CarneiroMargaridaMHeidelberg University Hospital, Medical Clinic 5, Rheumatology, HeidelbergauthorYangYangZhihuaZHeidelberg University Hospital, Medical Clinic 5, Rheumatology, HeidelbergauthorPietzckerPietzckerPhilippaPHeidelberg University Hospital, Medical Clinic 5, Rheumatology, HeidelbergauthorSongSongRuoyuRHeidelberg University Hospital, Medical Clinic 5, Rheumatology, HeidelbergauthorLuLuJunyanJHeidelberg University Hospital, Medical Clinic 5, Rheumatology, HeidelbergauthorLorenzLorenzHanns-MartinHMHeidelberg University Hospital, Medical Clinic 5, Rheumatology, HeidelbergauthorGerman Medical Science GMS Publishing House
Düsseldorf
61020250917englThis is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License.Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung).M0627029Deutsche Gesellschaft für RheumatologieDeutsche Gesellschaft für Orthopädische Rheumatologie53. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 39. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)Deutscher Rheumatologiekongress 2025Experimentelle & Translationale RheumatologieWiesbaden2025091720250920ET.08TextIntroduction: Recent thymic emigrants (RTEs) are a distinct subset of naïve T cells that have just exited the thymus and are essential for maintaining peripheral immune balance . Increasing evidence suggests that RTEs are highly responsive to inflammatory signals and may contribute to immune dysregulation . However, their specific role in the pathogenesis of rheumatoid arthritis (RA) remains unknown. In this study, we employed single-cell analysis to comprehensively characterize RTEs in RA.Methods: We analyzed single-cell RNA sequencing data3 from 36 clinical PBMC samples to construct a comprehensive atlas of RTEs in human RA. Gene set enrichment analysis was performed to score RTEs across different disease states and subtypes. Differential gene expression analysis and KEGG enrichment were conducted on RTEs and surrounding T cell subsets. Additionally, we investigated cell–cell communication, developmental trajectories, and metabolic features to delineate the functional landscape of RTEs in RA.Results: Our analysis revealed that CD8+ RTEs exhibited a more distinct RTE signature compared to CD4+ RTEs, with higher expression specificity for known markers—both in RA patients and healthy controls. Notably, in RA patients, differentially expressed genes in CD8+ RTEs were enriched in metabolism-related pathways such as the mTOR signaling pathway, fatty acid metabolism, and pentose phosphate pathway. In contrast, CD8+ RTEs in healthy controls showed enrichment in pathways like fructose and mannose metabolism. Further metabolic pathway analysis revealed that CD8+ RTEs in RA displayed higher levels of glycolysis and lipid metabolism compared to other subsets. Additionally, the synthesis of steroid hormones was found to be reduced (Figure 1 ). Cell–cell communication analysis further revealed that CD8+ RTEs accounted for 75% of key interaction events in RA (Figure 2 ). Among these, MHC-I-mediated signaling emerged as the predominant communication type, suggesting a pivotal role of antigen presentation and immune surveillance in the functional rewiring of CD8+ RTEs. Trajectory analysis indicated that CD8+ RTEs represent one of the earliest developmental T cell states, with activation levels positively correlated with age and CRP level.Conclusion: In rheumatoid arthritis, CD8+ RTEs represent a metabolically reprogrammed T cell subset with active participation in intercellular communication. Their functional dynamics may indicate disease progression and prognosis in RA.Ao YQJiang JHGao JWang HKDing JYRecent thymic emigrants as the bridge between thymoma and autoimmune diseases2022Biochim Biophys Acta Rev Cancer188730Ao YQ, Jiang JH, Gao J, Wang HK, Ding JY. Recent thymic emigrants as the bridge between thymoma and autoimmune diseases. Biochim Biophys Acta Rev Cancer. 2022 May;1877(3):188730. DOI: 10.1016/j.bbcan.2022.188730http://dx.doi.org/10.1016/j.bbcan.2022.188730Friesen TJJi QFink PJRecent thymic emigrants are tolerized in the absence of inflammation2016J Exp Med913-20Friesen TJ, Ji Q, Fink PJ. Recent thymic emigrants are tolerized in the absence of inflammation. J Exp Med. 2016;213(6):913-20. DOI: 10.1084/jem.20151990http://dx.doi.org/10.1084/jem.20151990Binvignat MMiao BYWibrand CYang MMRychkov DFlynn ENititham JTamaki WKhan UCarvidi AKrueger MNiemi ESun YFragiadakis GKSellam JMariotti-Ferrandiz EKlatzmann DGross AJYe CJButte AJCriswell LANakamura MCSirota MSingle-cell RNA-Seq analysis reveals cell subsets and gene signatures associated with rheumatoid arthritis disease activity2024JCI Insighte178499Binvignat M, Miao BY, Wibrand C, Yang MM, Rychkov D, Flynn E, Nititham J, Tamaki W, Khan U, Carvidi A, Krueger M, Niemi E, Sun Y, Fragiadakis GK, Sellam J, Mariotti-Ferrandiz E, Klatzmann D, Gross AJ, Ye CJ, Butte AJ, Criswell LA, Nakamura MC, Sirota M. Single-cell RNA-Seq analysis reveals cell subsets and gene signatures associated with rheumatoid arthritis disease activity. JCI Insight. 2024 Jul 2;9(16):e178499. DOI: 10.1172/jci.insight.178499http://dx.doi.org/10.1172/jci.insight.178499011
Figure 1: KEGG Enrichment pathways in Normal and RA samples
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Figure 2: Cell-cell communications in Normal and RA PBMC samples