Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), DRF, Francois Jacob Institute of Biology, Laboratory of Genomics and Radiobiology of Keratinopoiesis, Institute of Cellular and Molecular Radiobiology, Evry, France.
Université Paris-Saclay, Saint-Aubin, France.
Front Immunol. 2022 Feb 11;13:786859. doi: 10.3389/fimmu.2022.786859. eCollection 2022.
Preservation of a functional keratinocyte stem cell pool is essential to ensure the long-term maintenance of epidermis integrity, through continuous physiological renewal and regeneration in case of injury. Protecting stem cells from inflammation and immune reactions is thus a critical issue that needs to be explored. Here, we show that the immature CD49f precursor cell fraction from interfollicular epidermis keratinocytes, comprising stem cells and progenitors, is able to inhibit CD4 T-cell proliferation. Of note, both the stem cell-enriched CD49f/EGFR subpopulation and the less immature CD49f/EGFR progenitors ensure this effect. Moreover, we show that HLA-G and PD-L1 immune checkpoints are overexpressed in CD49f precursors, as compared to CD49f differentiated keratinocytes. This potency may limit immune reactions against immature precursors including stem cells, and protect them from exacerbated inflammation. Further exploring this correlation between immuno-modulation and immaturity may open perspectives in allogenic cell therapies.
保持功能性角蛋白干细胞池对于确保表皮完整性的长期维持至关重要，这是通过在受伤时进行持续的生理更新和再生来实现的。因此，保护干细胞免受炎症和免疫反应的影响是一个亟待探索的关键问题。在这里，我们表明，来自毛囊间表皮角质形成细胞的不成熟 CD49f 前体细胞群，包括干细胞和祖细胞，能够抑制 CD4+T 细胞的增殖。值得注意的是，富含干细胞的 CD49f/EGFR 亚群和较不成熟的 CD49f/EGFR 祖细胞都能确保这种作用。此外，我们还表明，与分化的 CD49f 角质形成细胞相比，HLA-G 和 PD-L1 免疫检查点在 CD49f 前体细胞中过度表达。这种能力可能限制了针对包括干细胞在内的不成熟前体细胞的免疫反应，并保护它们免受炎症加剧的影响。进一步探索这种免疫调节与不成熟之间的相关性，可能为同种异体细胞治疗开辟新的前景。
