POS1412 SINGLE-CELL ANALYSIS REVEALS THE PHENOTYPIC AND FUNCTIONAL HETEROGENEITY OF PERIPHERAL HELPER T CELLS IN THE SYNOVIUM OF RHEUMATOID ARTHRITIS
Notice bibliographique
Résumé
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied by synovitis and joint bone destruction. During the development of RA, the synovium undergoes hyperplasia and a large number of lymphocytes infiltrating, including CD4 + T cells and B cells. Specifically, a population of CD4 + PD1 hi CXCR5 - peripheral helper T cells (Tph) has been identified in the synovium and synovial fluid. The main function of this population is to promote the differentiation of plasma cells. However, it is unclear whether Tph could be further subdivided into subsets with different functions. Objectives: To extensively characterize the molecular, phenotypic and functional features of Tph subsets in RA synovium and to better understand the local immune microenvironment with therapeutic angle. Methods: Ten synovial tissues and paired blood were collected from active RA patients. CD3 + T cells were sorted and were subjected to scRNA-seq and scTCR-seq. Additional 25 synovial tissues from active RA patients were used for validation and functional experiments. scRNA-seq/scTCR-seq, flow cytometry and multiplex immunohistochemistry (mIHC) were used to define local immune microenvironment in synovium. B and T cell co-culture experiments were used to evaluate the effects of Tph subsets on plasma cell differentiation. Results: scRNA-seq classified synovial Tph cells into LAG3 - and LAG3 + subsets, which was validated by flow cytometry and mIHC. LAG3 - Tph mainly expressed molecules such as CD27, CCR7, TCF1, and LEF1, indicating that it was in the early stage of differentiation. Interestingly, LAG3 - Tph, but not LAG3 + Tph, highly expressed CXCL13. Spatial analysis indicated that LAG3 - Tph were located in proximity to CXCR5 + B cells. Functional analysis revealed that LAG3 - Tph, but not LAG3 + Tph, potently induced plasma cell differentiation. Compared with LAG3 - Tph, LAG3 + Tph highly expressed activation molecules such as HLADR and OX40, exhausted molecules such as TIGIT and CD39, and transcription factors such as MAF and BLIMP1, suggesting that LAG3 + Tph cells were in a state of over-activation prone to exhaustion. Consistently, pseudotime and TCR repertoire analyses indicated that LAG3 + Tph were located at the terminal with high clonal expansions. Conclusion: This study reveals the molecular, phenotypic and functional heterogeneity and differentiation relationship of LAG3 - and LAG3 + Tph subsets in RA joints. While the function of LAG3 + Tph needs further study, targeted inhibition of Tph differentiation may provide new therapeutic opportunities for RA. REFERENCES: NIL . Acknowledgements: This study is supported by Shanghai Municipal Science and Technology Committee of Shanghai Outstanding Academic Leaders Plan (No. 23XD1404300). Disclosure of Interests: None declared . © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».