Endoderm-Derived Myeloid-like Metaphocytes in Zebrafish Gill Mediate Soluble Antigen-Induced Immunity

Immune cells in the mucosal barriers of vertebrates are highly heterogeneous in their origin and function. This heterogeneity is further exemplified by the recent discovery of ectoderm-derived immune cells-metaphocytes in zebrafish epidermis. Yet, whether non-hematopoiesis-derived immune cells generally exist in barrier tissues remains obscured. Here, we report the identification and characterization of an endoderm-derived immune cell population in the gill and intestine of zebrafish. Transcriptome analysis reveals that the endoderm-derived immune cells are myeloid-like cells with high similarities to the ectoderm-derived metaphocytes in epidermis. Likemetaphocytes in epidermis, the endoderm-derived immune cells are non-phagocytic but professional in external soluble antigen uptake. Depletion of the endoderm-derived immune cells in gill hinder the local immune response to external soluble stimulants. This study demonstrates a general existence of non-hematopoiesis-derived immune cells in zebrafish mucosal barriers and challenges the prevalent view that resident immune cells in mucosal barriers arise exclusively from hematopoiesis.