FRI0354 ASSESSING THE ROLE OF TENDON-T CELL INTERACTIONS IN THE DEVELOPMENT OF CHRONICITY IN SPONDYLOARTHRITIS

Background Enthesitis is a hallmark of spondyloarthropaties[1], with mechanical stress or damage in the tendon being proposed as a trigger for the development of inflammation at the enthesis that propagates to the synovial compartment through what has been termed “synovio-enthesial complex”[2]. Increasing evidence supports the role that stromal cells play in the shift of the inflammatory process towards chronicity promoting T cell migration, retention and survival[3]. Therefore, we hypothesize that after tendon damage the crosstalk between stromal and immune compartments contributes to the development of chronic inflammation. Objectives We aimed to assess the effect of tendon stromal cells (tenocytes) on T cell migration and activation and the impact of these activated T cells on the stroma. Methods Tenocytes were explanted from tissue obtained from anterior cruciate ligament (ACL) reconstructions. The effect of damage on tenocytes after stimulation with conditioned media from tendon explants or IL-1s was evaluated by qPCR. A transwell membrane system was used to test the impact of conditioned media from tenocytes on T cell migration. T cells and tenocytes were co-cultured with or without the presence of a transwell membrane to quantify T cell activation (CD69 by FACS and IFN-γ by ELISA). Changes in gene expression on tenocytes after co-culture with activated T cells were analysed by qPCR. Results In the presence of damage, tenocytes upregulated inflammatory mediators (IL-6, COX2), chemokines (CCL2, CCL5, CXCL10, CXCL12) and adhesion molecules (ICAM-1). Conditioned media, particularly after stimulation with IL-1s, from tenocytes induced T cell migration. Co-cultures of tenocytes and T cells resulted in activation of T cells that was contact dependant. In turn, these activated T cells upregulated the production of inflammatory mediators in tenocytes and increased the COL3/COL1 ratio. Conclusion Our results support a communication between the stromal and immune compartment within the tendon that could be involved in the progression towards chronicity in the context of spondyloarthritis. Following damage, tendon stromal cells are able to induce the recruitment of T cells, that once enter the tissue interact with the stroma. Stromal cells are then further activated to produce inflammatory cytokines and chemokines that amplify and maintain this inflammatory response. References [1] G. Schett, et al., “Enthesitis: from pathophysiology to treatment,” Nat. Rev. Rheumatol., vol. 13, no. 12, pp. 731–741, 2017. [2] D. McGonagle, S. Z. Aydin, and A. L. Tan, “The synovio-entheseal complex and its role in tendon and capsular associated inflammation,” J. Rheumatol., vol. 39, no. SUPPL. 89, pp. 11–14, 2012. [3] C. D. Buckley, “Why does chronic inflammation persist: An unexpected role for fibroblasts,” Immunol. Lett., vol. 138, no. 1, pp. 12–14, 2011. Disclosure of Interests Emma Garcia-Melchor: None declared, Giacomo Cafaro: None declared, Lindsay AN Crowe: None declared, Michael McLean: None declared, James H Reilly: None declared, Iain McInnes Grant/research support from: AstraZeneca, Celgene, Compugen, Novartis, Roche, UCB Pharma, Consultant for: AbbVie, Celgene, Galvani, Lilly, Novartis, Pfizer, UCB Pharma, Moeed Akbar: None declared, Neal L Millar: None declared