542 Murine epidermis harbors functionally distinct langerhans cell subsets

نویسندگان

چکیده

Epidermal Langerhans cells (LCs) derive from embryonic myeloid progenitors at the steady-state and monocyte under inflammatory conditions. LCs have capacity to induce both immunity tolerance in skin, but how a single population of mediates these functions has perplexed researchers for decades. We hypothesized that murine epidermis functionally heterogenous subpopulations. employed single-cell RNA sequencing (scRNAseq) scATACseq identify transcriptional epigenetic heterogeneity during late development, adult inflamed-state. found three transcriptionally distinct clusters steady-state: ATF3hiCD207lo (cLC1), ATF3loCD207hi (cLC2), CD207+ expressing keratinocyte (KC) genes (kLCs). Ingenuity pathway analysis showed LC1 had downregulated immunostimulatory pathways LC2 upregulated pathways. ATF3 knockout mice promoted Th1/2/17 co-culture experiments, confirming immunotolerant function cLC1s. cLC1 cLC2 corresponding kLCs did not, suggesting may acquire their KC-“fingerprint” through interactions with KCs. scRNAseq analyses E18.5 pre-LCs 3 weeks post UVC-treatment also identified ATF3hi ATF3lo clusters, were neither present nor after UVC treatment. Overall, our cell uncover epidermal LC subsets

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ژورنال

عنوان ژورنال: Journal of Investigative Dermatology

سال: 2022

ISSN: ['1523-1747', '0022-202X']

DOI: https://doi.org/10.1016/j.jid.2022.05.552