Cell-Intrinsic Wnt4 Influences Conventional Dendritic Cell Fate Determination to Suppress Type 2 Immunity.

ABSTRACT: Whether conventional dendritic cells (cDC) acquire subset identity under direction of Wnt family glycoproteins is unknown. We demonstrate that Wnt4, a β-catenin-independent Wnt ligand, is produced by both hematopoietic and nonhematopoietic cells and is both necessary and sufficient for preconventional DC1/cDC1 maintenance. Whereas bone marrow cDC precursors undergo phosphoJNK/c-Jun activation upon Wnt4 treatment, loss of cDC Wnt4 in CD11c^CreWnt4^flox/flox mice impaired differentiation of CD24⁺, Clec9A⁺, CD103⁺ cDC1 compared with CD11c^Cre controls. Conversely, single-cell RNA sequencing analysis of bone marrow revealed a 2-fold increase in cDC2 gene signature genes, and flow cytometry demonstrated increased numbers of SIRP-α

SUBMITTER: Hung LY 

PROVIDER: S-EPMC6615948 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature