AUTHOR=Mestrallet Guillaume , Carosella Edgardo D. , Martin Michele T. , Rouas-Freiss Nathalie , Fortunel Nicolas O. , LeMaoult Joel 

TITLE=Immunosuppressive Properties of Epidermal Keratinocytes Differ According to Their Immaturity Status

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.786859

DOI=10.3389/fimmu.2022.786859

ISSN=1664-3224

ABSTRACT=<p>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<sup>high</sup> precursor cell fraction from interfollicular epidermis keratinocytes, comprising stem cells and progenitors, is able to inhibit CD4<bold><sup>+</sup></bold> T-cell proliferation. Of note, both the stem cell-enriched CD49f<sup>high</sup>/EGFR<sup>low</sup> subpopulation and the less immature CD49f<sup>high</sup>/EGFR<sup>high</sup> progenitors ensure this effect. Moreover, we show that HLA-G and PD-L1 immune checkpoints are overexpressed in CD49f<sup>high</sup> precursors, as compared to CD49f<sup>low</sup> 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.</p>