Document Type

Conference Proceeding

Publication Date


Publication Title

J Invest Dermatol


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





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