O22 Assessing the role of tendon T cell interactions in the development of chronicity in PsA

Abstract Background Mechanical stress or damage is a well-known inducer of inflammation in both psoriasis and psoriatic arthritis (PsA). The occurrence of microtrauma at enthesial sites, areas subjected to high mechanic stress, could explain the development of local inflammation (enthesitis) that further extends to the synovial tissue through what it is known synovio-entheseal complex. Current treatment strategies mainly target the immune compartment, however there is growing evidence for the role of the stroma in the development of chronic inflammation. Increasing attention has focused on the interaction between the stroma and immune system and its role in the initiation/development of tissue inflammatory chronicity. Our hypothesis is that stromal cells in the tendon or tenocytes, once activated, are able to recruit and activate T cells into the tendon, which in turn may have an effect on the stroma, altogether leading to chronicity. Methods We assessed the effect of damage on healthy tenocytes after stimulation with conditioned media from tendon explants or IL-1β by qPCR and ELISA. 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 cytokines (IL-1β, IL-6), chemokines (IL-8, CCL2, CCL5, CXCL10) and adhesion molecules (ICAM-1). Of interest, we observed an upregulation of CCL20, both at transcript and protein level. Conditioned media from tenocytes induced T cell migration, especially after stimulation. Co-culture of tenocytes and T cells resulted in contact dependant activation of T cells. These activated T cells also had an effect on tenocytes, further upregulating the production of inflammatory mediators. Conclusion These results support the role of the tendon stromal compartment in the recruitment and activation of T cells, creating a feedback loop that could be involved in the maintenance of the inflammatory process and the development of chronicity in the context of PsA. Moreover, the production of CCL20 by tenocytes after damage could explain the preferential recruitment of Th17 or gamma delta T cells into the tendon. We are further investigating the mechanisms that govern this relationship that could be targeted therapeutically in the future. Disclosures E. Garcia-Melchor None. G. Cafaro None. S. Sood None. L.A.N. Crowe None. M. McLean None. I.B. McInnes None. M. Akbar None. N.L. Millar None.