Differential developmental requirement and peripheral regulation for dermal Vγ4 and Vγ6T17 cells in health and inflammation

Dermal IL-17-producing gdT cells have a critical role in skin inflammation. However, their development and peripheral regulation have not been fully elucidated. Here we demonstrate that dermal gdT cells develop from the embryonic thymus and undergo homeostatic proliferation after birth with diversified TCR repertoire. Vg6T cells are bona fide resident, but precursors of dermal Vg4T cells may require extrathymic environment for imprinting skinhoming properties. Thymic Vg6T cells are more competitive than Vg4 for dermal gdT cell reconstitution and TCRd -/- mice reconstituted with Vg6 develop psoriasis-like inflammation after IMQ-application. Although both IL-23 and IL-1b promote Vg4 and Vg6 proliferation, Vg4 are the main source of IL-17 production that requires IL-1 signalling. Mice with deficiency of IL-1RI signalling have significantly decreased skin inflammation. These studies reveal a differential developmental requirement and peripheral regulation for dermal Vg6 and Vg4 gdT cells, implying a new mechanism that may be involved in skin inflammation.