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Li-Yin Hung, John L Johnson, Yingbiao Ji, David A Christian, Karl R Herbine, Christopher F Pastore, De’Broski R Herbert, Wnt4 controls early cDC1 commitment to suppress Type 2 immunity, The Journal of Immunology, Volume 202, Issue 1_Supplement, May 2019, Page 190.44, https://doi.org/10.4049/jimmunol.202.Supp.190.44
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Abstract
Whether conventional dendritic cells (cDC) acquire subset identity under direction of regenerative glycoproteins is unknown. We demonstrate that Wnt4, a beta-catenin independent Wnt ligand, is necessary and sufficient for pre-cDC1 BM specification. CD11c-restricted Wnt4 deficiency reduced mature cDC1 numbers in BM, spleen, lung, and intestine and Wnt4 directly induced of pJNK activation and cDC1 commitment. CD11cCre Wnt4 flox/flox mice lacked IRF8/cJun complex stabilization and had increased basal numbers of cDC2, group 2 innate lymphoid cells ILC2 and increased resistance to the parasite Nippostrongylus brasiliensis compared to CD11cCre controls. These data reveal a novel role for Wnt4 in DC commitment and pathogen-specific immunity.