2020; Tung et al. 2020). In the present study, we demonstrated that Tregs induced with polarising cytokines in the presence of retinoic acid (RATregs) secrete CD73+ EVs, which generate adenosine upon AMP exposure. Importantly, these EVs suppressed the activation and proliferation of effector CD4+ T cells, in part through the action of the CD73/ADO pathway. Additionally, RATEVs modulated IL‐17A+ and RANKL+ CD4+ T cell‐mediated periodontal immune dysregulation, inhibited osteoclastogenesis and mitigated tooth‐supporting alveolar bone loss during experimental periodontitis (Figure 7). Here, CD4 is linked to periodontitis.