PD-L1⁺ Neutrophils Mediate Immune Regulation of CD8⁺ T Cells in Halo Nevi

Halo nevi are clinically common and are characterized by a circle of leukoderma around the central melanocytic nevus. Studies have shown that the pathogenesis of the surrounding leukoderma is similar to that of vitiligo and is associated with the role of CD8⁺ T lymphocytes in melanocyte destruction. Notably, some halo nevi exhibit a tendency for spontaneous regression of the surrounding leukoderma, yet the underlying mechanisms remain unclear. Furthermore, histopathological findings have revealed neutrophil infiltration in halo nevi, but the specific immune mechanisms involving neutrophils have not been thoroughly investigated. This study investigated the role of neutrophils in halo nevi through histopathological and immunological analyses, aiming to provide some clues for identifying the mechanisms underlying the regression of surrounding leukoderma. We examined the infiltration patterns of immune cells in halo nevi, with a particular focus on IFN-γ-induced PD-L1 expression in neutrophils and its potential immunoregulatory effects. The results demonstrated that IFN-γ expression in the lesional skin of halo nevi contributed to the induction of PD-L1 expression in neutrophils. PD-L1⁺ neutrophils promoted apoptosis and suppressed the function of CD8⁺ T lymphocytes. This regulatory mechanism influences the local immune response and may facilitate the repigmentation of the surrounding leukoderma. This study is the first to explore the involvement mechanism of neutrophils in halo nevi and to reveal the potential immunoregulatory role of PD-L1. The elucidation of this mechanism not only provides a more comprehensive understanding of autoimmune skin diseases but may also offer new strategies for targeted therapy in related pigmentary disorders, such as vitiligo.