DOI: 10.1101/469155Nov 14, 2018Paper

Cell-intrinsic Wnt4 controls early cDC1 commitment and suppresses development of pathogen-specific Type 2 immunity

BioRxiv : the Preprint Server for Biology
Li-Yin HungDe'Broski R Herbert

Abstract

Whether conventional dendritic cell (cDC) precursors acquire lineage-specific identity under direction of regenerative secreted glycoproteins within bone marrow niches is entirely unknown. Herein, we demonstrate that Wnt4, a beta-catenin independent Wnt ligand, is both necessary and sufficient for necessary for the full extent of pre-cDC1 specification within bone marrow. Cell-intrinsic Wnt4 deficiency in CD11c+ cells reduced mature cDC1 numbers in BM, spleen, lung, and intestine and, reciprocally, rWnt4 treatment promoted pJNK activation and cDC1 expansion. Lack of cell-intrinsic Wnt4 in mice CD11cCreWnt4flox/flox impaired stabilization of IRF8/cJun complexes in BM and increased the basal frequency of both cDC2 and ILC2 populations in the periphery. Accordingly, CD11c-restricted Wnt4 augmented Type 2 immunity against the hookworm parasite Nippostrongylus brasiliensis accompanied by increased interleukin 5 production relative to CD11cCre controls. Collectively, these data show previously unappreciated role for Wnt4 in DC commitment and pathogen-specific immunity.

Related Concepts

Bone Marrow
Cell Growth
Dendritic Cells
Glycoproteins
Interleukins
Intestines
CD11c Antigens
Ligands
Lung
Laboratory mice

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