cDC2 subsets

Cell 179, 846–863.e24 (2019)

Classical dendritic cells are classified as cDC1 and cDC2 on the basis of their function and dependence on transcription factors. In Cell, Rudensky and colleagues describe two distinct subsets of cDC2s in mice and humans. Through the use of Tbx21^RFP-Cre reporter mice and single-cell RNA sequencing, the authors identify a subpopulation of T-bet⁺ cDC2s that express a core set of 69 genes, including Tbx21, Dtx1 and Ccr6. A distinct subset of T-bet^– cDC2s express Rorc, Tmem176a, Tmem176b, Clec12a, Cx3cr1, Cd14, Il1a and P2rx7. cDC2s acquire these specific transcriptional profiles in the periphery, probably in response to signals from the tissue microenvironment. The two cDC2 subsets express distinct patterns of genes encoding Toll-like receptors, chemokines and chemokine receptors. T-bet^– cDC2s have a more pro-inflammatory profile, while T-bet⁺ cDC2s express transcripts encoding molecules involved in tissue repair and have a diminished ability to polarize naive T cells. On the basis of single-cell RNA sequencing of spleen and blood cells, human CD1c^loCLEC10A^–CLEC4A^hi cDC2s and CD1c⁺CLEC10A⁺CLEC4A^lo cDC2s are the equivalent of mouse T-bet⁺ cDC2s (designated ‘cDC2A’) and T-bet^– cDC2s (‘cDC2B’), respectively.