Specifically inhibiting SOX5 in enthesis fibroblasts via rAAV9.HAP-1 carrying a shRNA targeting Sox5 blocked the generation of SDC1<sup>+</sup> sheath fibroblasts in response to mechanical strain and markedly reversed the development of CXCR4<sup>hi</sup> neutrophil-mediated enthesitis. This evidence concerns the gene SOX5 and enthesitis.