An Ectoderm-Derived Myeloid-like Cell Population Functions as Antigen Transporters for Langerhans Cells in Zebrafish...

Tissue-resident macrophages (TRMs) are highly heterogeneous and engage in a wide range of diverse functions. Yet, the heterogeneities of their origins and functions remain incompletely defined. Here, we report the identification and characterization of an ectoderm-derived myeloid-like cell, which we refer to as metaphocyte. We show that metaphocytes are highly similar to conventional Langerhans cells (cLCs), the resident macrophages in epidermis, in transcriptome, morphology, and anatomic location. However, unlike cLCs, metaphocytes respond neither to tissue injury nor to bacterial infection but rather sample soluble antigens from external environment through transepithelial protrusions and transfer them to cLCs via apoptosis-phagocytosis axis. This antigen transfer is critical for zebrafish to respond to soluble antigens because the depletion of metaphocytes significantly reduces cLC antigen uptake. Our study documents the existence of ectoderm-derived myeloid-like cells that manifest distinct function from conventional TRMs and opens a new paradigm for investigation of the heterogeneities of resident immune cells.