Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: While the exact pathogenesis of psoriatic arthritis (PsA) remains unclear, it is recognised that several environmental factors operate in individuals with genetic susceptibility leading to sustained inflammatory responses. These involve both the innate and adaptive immune system with IL23/IL17 axis playing a central role. One suggested environmental factor is mechanical stress and accordingly, involvement of entheseal sites exposed to maximal biomechanical loading is a common feature of PsA. However, the mechanisms linking mechanical stress/damage at the enthesis/tendon which leads to immune cell activation remains unknown. We aimed to interrogate the role of tendon stromal cells (tenocytes) in the induction of a type 17 response.
Methods: Immunohistochemical staining for CCR6 was performed in paraffin embedded PsA synovial membrane and the presence of CCL20 was quantified in synovial fluid (SF) from PsA and osteoarthritis (OA) patients by ELISA. Healthy tenocytes cultured from hamstring tendons and fibroblast-like synoviocytes (FLS) from PsA patients were stimulated with human IL-1β (1 ng/ml) and IL-17A (1, 10 and 100 ng/ml). Expression of CCL20 transcript and protein upon stimulation were assessed by qPCR and ELISA, respectively. T cell migration assays were performed with magnetically enriched CD3+ cells from peripheral blood of PsA patients and healthy controls using a Transwell system.
Results: We observed an abundance of CCR6 positive cells in PsA synovial membrane and higher levels of CCL20 in SF from PsA patients compared with OA (OA mean+/-SEM 40.91+/-30.06 pg/ml, n=14; PsA 339.5+/-100.7 pg/ml, n=39; p<0.0001). Tenocytes were able to upregulate CCL20 transcript (fold change 680.5+/-215.2; p<0.0001, n=5) and produce CCL20 (481.8+/- 84.26 pg/ml; p<0.0001, n=13), following stimulation with IL-1β. In this context, the addition of IL-17A induced a synergistic effect with IL-1β in both tenocytes and PsA FLS. Conditioned media from tenocytes promoted T cell migration.
Conclusion: Activated tendon stromal cells and PsA synovial fibroblasts are able to produce CCL20, a chemokine that binds to CCR6 and is responsible for the recruitment of IL-17 producing cells. In conclusion, our results support a role of the tendon stromal compartment in the development of a type 17 immune response in PsA.
To cite this abstract in AMA style:Garcia-Melchor E, Cafaro G, Akbar M, Gilchrist D, Kitson SM, Siebert S, McInnes IB, Millar NL. Activated Tendon Stromal Cells Drive a Type 17 Immune Response Via CCL20: A Potential Role in the Pathogenesis of Enthesitis in Psoriatic Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/activated-tendon-stromal-cells-drive-a-type-17-immune-response-via-ccl20-a-potential-role-in-the-pathogenesis-of-enthesitis-in-psoriatic-arthritis/. Accessed October 28, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/activated-tendon-stromal-cells-drive-a-type-17-immune-response-via-ccl20-a-potential-role-in-the-pathogenesis-of-enthesitis-in-psoriatic-arthritis/