Identification of natural killer cells and innate lymphoid cells in human epidermis

Summary: Abstract Body: Resident memory T cells and resident memory regulatory T cells have been identified in the human epidermis. Meanwhile, it has been largely unknown whether innate immune cells such as natural killer (NK) cells and innate lymphoid cells (ILCs) are present in the human epidermis. Hence, this study sought to identify them and examine their function. The following three innate immune cells were identified based on the expression of CD94 and CD127: CD94+CD127− NK cells, CD94+CD127+ cytotoxic ILCs (cytoILCs), and CD94−CD127+ conventional ILCs (convILCs). In the CD45+Lin− cells of PBMC, NK cells were the predominant innate immune cells. In the epidermal CD45+CD3− lymphocytes, three populations of innate immune cells were identified. However, unlike PBMC, convILCs were the predominant innate immune cells. A transcriptional factor Eomes is essential for the development, proliferation, and persistence of human NK cells. Additionally, Eomes-depleted human NK cells change the phenotype to ILC. NK cells in PBMC almost completely express Eomes. Epidermal NK cells exhibited higher Eomes expression than cyto ILCs and convILCs. However, its expression rate was only about 20%. These data suggest that under the conditions of the epidermis, the expression of Eomes in NK cells decreases due to some kind of influence, causing a decrease in the number of cells and/or their conversion to ILCs. All three epidermal innate immune cells strongly express skin retention markers such as CLA and CD69. Moreover, the percentage of CD103+CD49a+ cells in CD69+ cells was significantly greater in epidermal innate immune cells compared to those in dermal counterparts. Functionally, epidermal NK cells produced much greater perforin than two ILC populations, however their killing activities were much weaker than those of PBMC NK cells. In summary, we identify innate immune cells in the human epidermis, suggesting that the epidermis is not only endowed with acquired immune cells, but also with innate immune cells like the dermis. However, their function is suppressed. Youichi Ogawa¹, Takuya Sato¹, Shinji Shimada¹, Tatsuyoshi Kawamura¹ 1. Dermatology, Yamanashi Daigaku Igakubu Daigakuin Sogo Kenkyubu Igakuiki, Chuo, Yamanashi Prefecture, Japan. Innate Immunity, Microbiology, and Microbiome