Cell-Intrinsic Wnt4 Influences Conventional Dendritic Cell Fate Determination to Suppress Type 2 Immunity.
Li-Yin HungJohn L JohnsonYingbiao JiDavid A ChristianKarl R HerbineChristopher F PastoreDe'Broski R HerbertPublished in: Journal of immunology (Baltimore, Md. : 1950) (2019)
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 CD11cCreWnt4flox/flox mice impaired differentiation of CD24+, Clec9A+, CD103+ cDC1 compared with CD11cCre 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+ cDC2 amid lack of Wnt4. Increased cDC2 numbers due to CD11c-restricted Wnt4 deficiency increased IL-5 production, group 2 innate lymphoid cell expansion, and host resistance to the hookworm parasite Nippostrongylus brasiliensis Collectively, these data uncover a novel and unexpected role for Wnt4 in cDC subset differentiation and type 2 immunity.
Keyphrases
- cell proliferation
- single cell
- dendritic cells
- cell cycle
- stem cells
- bone marrow
- rna seq
- immune response
- flow cytometry
- gene expression
- machine learning
- nk cells
- type diabetes
- epithelial mesenchymal transition
- oxidative stress
- regulatory t cells
- induced apoptosis
- metabolic syndrome
- big data
- transcription factor
- insulin resistance
- mass spectrometry
- signaling pathway
- copy number
- deep learning
- pi k akt
- solid phase extraction
- liquid chromatography
- cell cycle arrest