Spondyloarthritis (SpA) is a chronic immune-mediated inflammatory disease affecting not only the joints and entheses, but also barrier tissues: gastrointestinal tract, skin and the eye. γδ T cells, a population of innate-like T lymphocytes, play a crucial role in the SpA pathology. In this project, we aim to investigate the functional phenotype γδ T cells in SpA through the prism of unresolved, clinically-relevant questions. It is not clear if the mechanisms driving chronic inflammation in SpA are common or distinct across tissues, and whether this could account for the differential response to treatment among patients. We will address this issue by deep functional- and immunophenotyping of γδ T cells from the gut, joint and peripheral blood of well-characterized, treatment-naïve SpA patients. We will longitudinally assess these immune milieux in an established mouse model of SpA. Recirculation of immune cells between the gut and joints will be interrogated in transgenic mice expressing a photo-convertible Kaede fluorochrome. Lastly, we will assess the role of epigenetic modulation of the γδ T cell phenotype plasticity in SpA, potentially determining the chance of achieving drug-free remission. Therefore, the acquired basic immunology data will be analyzed in the context of therapeutic outcomes in a clinical trial setting. This study will provide a detailed picture of aberrant γδ T cell characteristics in SpA-affected tissues and their potential role in therapeutic responses.