A1.2 Prominent role of pathogenic memory CCR6+ TH17 cell populations in the pathogenesis of ACPA+ patients with rheumatoid arthritis
| Autor: | N Davelaar, Smj Paulissen, E Lubberts, Wendy Dankers, Jmw Hazes, JP van Hamburg, Php de Jong, Heleen Vroman |
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| Rok vydání: | 2015 |
| Předmět: |
musculoskeletal diseases
TBX21 biology business.industry medicine.medical_treatment Immunology chemical and pharmacologic phenomena hemic and immune systems C-C chemokine receptor type 6 CXCR3 General Biochemistry Genetics and Molecular Biology Pathogenesis Cytokine Rheumatology immune system diseases RAR-related orphan receptor gamma biology.protein Immunology and Allergy Medicine Synovial fluid Antibody skin and connective tissue diseases business |
| Zdroj: | Annals of the Rheumatic Diseases. 74:A1.2-A1 |
| ISSN: | 1468-2060 0003-4967 |
| DOI: | 10.1136/annrheumdis-2015-207259.2 |
| Popis: | Background and objectives Patients with rheumatoid arthritis (RA) positive for serum anti-citrullinated protein antibodies (ACPAs) have a worse disease course than ACPA- patients. Association of ACPA and HLA-DRB1 suggests the involvement of T cells in ACPA+ RA. Therefore we examined possible differences in memory CD4 + T (Th) cell distribution between ACPA+ and ACPA- patients and their functional relevance. Materials and methods Th cell distribution profiles from ACPA+ and ACPA- patients with early RA were generated based on chemokine receptor, cytokine and transcription factor expression. On the basis of CXCR3 and CCR4 expression, four CCR6+ subpopulations were distinguished: Th17, Th17.1, CCR4/CXCR3 double positive (DP) and double negative (DN) cells. These Th cell populations were analysed for their pathological potential. Results ACPA+ patients had higher proportions of peripheral CCR6+ Th cells, notably Th22, Th17.1 and DP cells. All CCR6+ subpopulations were also present in RA synovial fluid. These subpopulations shared Th17 characteristics including RORC and CD161 expression. However, expression of IL-17A, IL-17F, IFNg and the Th1-associated transcription factor TBX21 differed markedly between CCR6+ subpopulations. Nevertheless, all CCR6+ Th cell subpopulations showed higher pathological activity than naive and Th1 cells, as they were more effective in stimulating IL-1β, IL-6, IL-8, COX-2 and MMP-3 expression by synovial fibroblasts. Interestingly, CCR6+ Th populations are inverse correlated with disease duration in ACPA- patients but not in ACPA+ patients. Conclusions ACPA+ and ACPA- patients can be distinguished by differences in pathogenic memory CCR6+ Th cell proportions, suggesting that these cells are involved in the worse disease course observed in ACPA+ RA. |
| Databáze: | OpenAIRE |
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