CEA, Laboratory of Genomics and Radiobiology of Keratinopoiesis, Institute of Cellular and Molecular Radiobiology, Francois Jacob Institute of Biology, DRF, 91000 Evry, France.
Université Paris-Saclay, 91190 Saint-Aubin, France.
Cells. 2021 Jun 8;10(6):1438. doi: 10.3390/cells10061438.
Human skin protects the body against infection and injury. This protection involves immune and epithelial cells, but their interactions remain largely unknown. Here, we show that cultured epidermal keratinocytes inhibit allogenic CD4 T-cell proliferation under both normal and inflammatory conditions. Inhibition occurs through the secretion of soluble factors, including TGFB1 and the cell-surface expression of HLA-G1 and PD-L1 immune checkpoints. For the first time, we here describe the expression of the HLA-G1 protein in healthy human skin and its role in keratinocyte-driven tissue immunomodulation. The overexpression of HLA-G1 with an inducible vector increased the immunosuppressive properties of keratinocytes, opening up perspectives for their use in allogeneic settings for cell therapy.
人类皮肤可以保护身体免受感染和损伤。这种保护作用涉及免疫细胞和上皮细胞，但它们之间的相互作用在很大程度上尚不清楚。在这里，我们表明，在正常和炎症条件下，培养的表皮角质形成细胞均能抑制同种异体 CD4 T 细胞的增殖。这种抑制作用是通过分泌可溶性因子实现的，包括 TGFB1 以及 HLA-G1 和 PD-L1 免疫检查点的细胞表面表达。我们首次在这里描述了 HLA-G1 蛋白在健康人类皮肤中的表达及其在角质形成细胞驱动的组织免疫调节中的作用。用诱导型载体过表达 HLA-G1 增加了角质形成细胞的免疫抑制特性，为其在同种异体细胞治疗环境中的应用开辟了新的前景。
