Two Distinct Types of Langerhans Cells Populate the Skin during Steady State and Inflammation

SummaryLangerhans cells (LCs), the dendritic cells (DCs) in skin epidermis, possess an exceptional life cycle and developmental origin. Here we identified two types of LCs, short-term and long-term LCs, which transiently or stably reconstitute the LC compartment, respectively. Short-term LCs developed from Gr-1hi monocytes under inflammatory conditions and occurred independently of the transcription factor Id2. Long-term LCs arose from bone marrow in steady state and were critically dependent on Id2. Surface marker and gene expression analysis positioned short-term LCs close to Gr-1hi monocytes, which is indicative of their monocytic origin. We also show that LC reconstitution after UV light exposure occurs in two waves: an initial fast and transient wave of Gr-1hi monocyte-derived short-term LCs is followed by a second wave of steady-state precursor-derived long-term LCs. Our data demonstrate the presence of two types of LCs that develop through different pathways in inflammation and steady state.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (249 K)Download as PowerPoint slideHighlights► Two types of Langerhans cells, short-term and long-term LCs, develop independently ► Gr-1hi monocytes are precursors for short-term LCs only in inflammation ► Adult bone marrow contains a precursor for long-term LC reconstitution ► LC reconstitution after inflammation occurs in two waves