Skin commensal Staphylococcus promotes systemic reconfiguration of Vγ6+ γδT cells

This study demonstrates that topical skin colonization with live S. aureus robustly expands IL-17-producing Vγ6⁺ γδT17 cells both locally in the dermis and across distant tissues, including mucosal, lymphoid, and metabolic organs. This systemic reconfiguration is IL-1R-dependent yet independent of IL-23, TLR2, or the microbiota.

Transcriptomic profiling reveals a transitional state in dermal Vγ6⁺ γδT cells, marked by changes in tissue-residency and migration-associated genes. Local proliferation, lymphatic trafficking and long-term recirculation sustain this response, even without systemic bacterial dissemination. These findings uncover a previously unrecognized allostatic process by which localized microbial signals recalibrate systemic immunological setpoints.