Clec12A, CD301b, and FcγRIIB/III define the heterogeneity of murine DC2s and DC3s
Lukas Amon, Anna Seichter, Damir Vurnek, Lukas Heger, Lukas Lächele, Nounagnon Romaric Tochoedo, Tomasz Kaszubowski, Lukas Hatscher, Anna Barańska, Giorgi Tchitashvili, Falk Nimmerjahn, Christian H.K. Lehmann, Diana Dudziak
Abstract
Over the last decade, multiple studies have investigated the heterogeneity of murine conventional dendritic cells type 2 (cDC2s). However, their phenotypic similarity with monocytes and macrophages renders their clear identification challenging. By creating a protein atlas utilizing multiparameter flow cytometry, we show that ESAM + cDC2s are a specialized feature of the spleen strongly differing in their proteome from other cDC2s. In contrast, all other tissues are populated by Clec12A + cDC2s or Clec12A − cDC2s (high or low for Fcγ receptors, C-type lectin receptors, and CD11b, respectively), rendering Clec12A + cDC2s classical sentinels. Further, expression analysis of CD301b, Clec12A, and FcγRIIB/III provides a conserved definition of cDC2 heterogeneity, including the discovery of putative FcγRIIB/III + DC3s across tissues. Finally, our data reveal that cell identity (ontogeny) dictates the proteome that is further fine-tuned by the tissue environment on macrophages and dendritic cells (DCs), while monocytes and plasmacytoid DCs (pDCs) display subset intrinsic default settings.