Immunoregulatory Microenvironment in the Elderly Skin

Abstract

Previous studies have revealed that skin T cells accumulate and maintain immune responses in the elderly. However, we questioned why these functional T cells fail to recognize and eliminate malignant cells, making elderly skin more prone to developing malignant tumors. To address this question, we examined the overall skin microenvironment in aging using the Nanostring nCounter system and 10x Xenium digital spatial RNA sequencing. The digital RNA counts of CIITA and HLA-DMA, which are involved in antigen presentation, were negatively correlated with age, whereas the counts of UBE2L3 and SOCS1, molecules that play roles in immune regulation, were positively correlated with aging. The upregulation of SOCS1 was detected in the microenvironment of the skin malignant tumors. Spatial transcriptome analysis revealed that cells with high levels of SOCS1 were distributed in upper dermis and periadnexal area, and some SOCS1-positive fibroblasts were closely lined with CD163-positive macrophages. Our study showed that the skin microenvironment in the elderly may shift to an immunoregulatory condition. Furthermore, modulating certain molecules that may be involved in shared immunoregulatory mechanisms between healthy elderly skin and malignant tumors could serve as a potential strategy for preventing malignancies in elderly skin.