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

J Immunol. 2019 Jul 15;203(2):511-519. doi: 10.4049/jimmunol.1900363. Epub 2019 Jun 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • CD11c Antigen / immunology
  • CD24 Antigen / immunology
  • Cell Differentiation / immunology
  • Dendritic Cells / immunology*
  • Flow Cytometry / methods
  • Immunity, Innate / immunology*
  • Integrin alpha Chains / immunology
  • Lymphocytes / immunology
  • Mice
  • Signal Transduction / immunology
  • Wnt4 Protein / immunology*
  • beta Catenin / immunology


  • Antigens, CD
  • CD11c Antigen
  • CD24 Antigen
  • Integrin alpha Chains
  • Wnt4 Protein
  • Wnt4 protein, mouse
  • alpha E integrins
  • beta Catenin