Conventional dendritic cells of lymphoid origin with a preferential distribution to barrier tissues [donor cDCs_RNA-seq]

Conventional dendritic cells (cDCs) regulate adaptive immunity. Although cDCs emerged with the evolution of adaptive immunity, it is considered that most cDCs are of myeloid origin (M-cDCs). Using a lymphoid progenitor-tracking system, we identify novel cDCs of lymphoid origin (L-cDCs) in a steady state. Notably, L-cDC2s are predominantly distributed in barrier tissues such as the lungs and skin. Single-cell RNA-sequencing analysis revealed that the distribution and gene expression patterns of L-cDC clusters are very similar to M-cDC clusters, except for the enrichment of lymphocyte-signature genes in L-cDCs. Importantly, we identified lymphoid-derived pre-DCs and lymphocyte-primed cDC precursors as sources of L-cDCs. Compared with M-cDC2s, L-cDC2s weakly primed T cells under low-dose antigen stimulation and preferentially promoted Th2 differentiation under sufficient antigenic stimulation. These results suggest the developmental diversity of cDCs and imply the contribution of L-cDCs to tolerance and hyper-responses to Th2-related antigens in barrier tissues. Overall design: To examine similarlity of CLP-derived cDC2s and L-cDC2s, we transferred CLPs or CDPs from wild-type (WT) mice (CD45.2+) into the BM of B6.SJL mice (CD45.1+). Four days after LPS treatment, CLP-derived cDC2s (CLP-cDC2s) and CDP-derived cDC2s (CDP-cDC2s) were isolated from the spleens for transcriptome analysis. We also isolated L-cDC2s (tdTomato+) and M-cDC2s (tdTomato-) from the spleens of Il7r-Cre;Rosa26-lsl-tdTomato mice 4 days after LPS treatment to compare their gene expression profiles with CLP-cDC2s and CDP-cDC2s.