Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma

The skin harbors a variety of resident leukocyte subsets that must be tightly regulated to maintain immune homeostasis. Hair follicles are unique structures in the skin that contribute to skin dendritic cell homeostasis via chemokine production. We demonstrate that CD4(+) and CD8(+) skin resident memory T cells (T(RM)), responsible for long-term skin immunity, resided predominantly within the hair follicle epithelium of unperturbed epidermis. T(RM) tropism for the epidermis and follicles was herein termed epidermotropism. Hair follicle-derived IL-15 was required for CD8(+) T(RM), and IL-7 for CD8(+) and CD4(+) T(RM), to exert epidermotropism. The lack of either cytokine impaired hapten-induced contact hypersensitivity responses. In a model of cutaneous T cell lymphoma, epidermotropic CD4(+) T(RM) lymphoma cell localization depended on hair follicle-derived IL-7. These findings implicate hair follicle-derived cytokines as regulators of malignant and non-malignant T(RM) cell tissue residence and suggest they may be targeted therapeutically in inflammatory skin disease and lymphoma.