POS1412 SINGLE-CELL ANALYSIS REVEALS THE PHENOTYPIC AND FUNCTIONAL HETEROGENEITY OF PERIPHERAL HELPER T CELLS IN THE SYNOVIUM OF RHEUMATOID ARTHRITIS
Bibliographic record
Abstract
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".