Subtype of macrophages and its clinical significance in Riehl’s melanosis

Summary: The phagocytosis of melanin granules by macrophages and the subsequent formation of melanophages are key histopathological features of Riehl’s melanosis. However, the role and underlying mechanisms of macrophages and phagocytes in disease progression remain unclear. To elucidate this, we performed single-cell RNA sequencing to characterize the immune landscape of Riehl’s melanosis and analyze the phenotypic and functional diversity of macrophage and melanophage subtypes. Our analysis identified seven macrophage subpopulations, among which MFI-FOLR2+ and MFI-CCR7+ macrophages may actively interact with melanocytes and T/NK cells. Histological examination using H&E and immunofluorescence staining of skin lesion samples revealed that infiltrating macrophages predominantly localize in the dermal papillae, sites of melanin deposition, and around the superficial capillary network. These macrophages exhibit a CD68+ CD86− CD206+ phenotype. Functionally, M1-conditioned medium inhibited melanin synthesis in melanocytes, whereas M2-conditioned medium promoted it. Furthermore, macrophages were more likely to undergo classical and alternative activation in a high LA/ALA ratio environment, whereas a low LA/ALA ratio favored a resting state. In conclusion, macrophage infiltration may serve as an auxiliary indicator for assessing pigmentation severity and prognosis in patients with Riehl’s melanosis. Chen Wang¹, Zhongyi Xu¹, Chengfeng Zhang¹, Leihong Xiang¹ 1. Dermatology, Huashan Hospital Fudan University, Shanghai, Shanghai, China. Pigmentation, Melanoma, and Melanoma Immune Surveillance