| First Author | Hung LY | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 2 | Pages | 511-519 |
| PubMed ID | 31175162 | Mgi Jnum | J:278507 |
| Mgi Id | MGI:6323748 | Doi | 10.4049/jimmunol.1900363 |
| Citation | Hung LY, et al. (2019) Cell-Intrinsic Wnt4 Influences Conventional Dendritic Cell Fate Determination to Suppress Type 2 Immunity. J Immunol 203(2):511-519 |
| abstractText | Whether conventional dendritic cells (cDC) acquire subset identity under direction of Wnt family glycoproteins is unknown. We demonstrate that Wnt4, a beta-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(Cre)Wnt4(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-alpha(+) 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. |
