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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE272703 | GEO | 2025/05/01

REPOSITORIES: GEO

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Project description:Dendritic cells (DCs) in lymphoid tissue comprise conventional DCs (cDCs) and plasmacytoid DCs (pDCs) that develop from common DC progenitors (CDPs). CDPs are Flt3+c-kitintM-CSFR+ and reside in bone marrow. Here we describe a two-step culture system that recapitulates DC development from c-kithiFlt3-/lo multipotent progenitors (MPPs) into CDPs and further into cDC and pDC subsets. MPPs and CDPs are amplified in vitro with Flt3 ligand, stem cell factor, hyper-IL-6 and insulin- like growth factor-1. The four-factor cocktail readily induces self-renewal of MPPs and their progression into CDPs and has no self-renewal activity on CDPs. The amplified CDPs respond to all known DC poietins and generate all lymphoid tissue DCs in vivo and in vitro. Additionally, in vitro CDPs recapitulate the cell surface marker and gene expression profile of in vivo CDPs and possess a DC-primed transcription profile. Transforming growth factor-Î²1 (TGF-Î²1) impacts on CDPs and directs their differentiation towards cDCs. Genome-wide gene expression profiling of TGF-Î²1-induced genes identified transcription factors, such as interferon regulatory factor-4 (IRF-4) and RelB, that are implicated as instructive factors for cDC subset specification. TGF-Î²1 also induced the transcription factor inhibitor of differentiation/DNA binding 2 (Id2) that suppresses pDC development. Thus, TGF-Î²1 directs CDP differentiation into cDC by inducing both cDC instructive factors and pDC inhibitory factors. 20 samples in total. Multipotent progenitor - MPP_1 - MPP_2 Common dendritic cell progenitor - CDP_1 - CDP_2 Plasmacytoid dendritic cell - pDC_1 - pDC_2 Conventional dendritic cell - cDC_1 - cDC_2 In vivo common dendritic cell progenitor - In vivo CDP_1 - In vivo CDP_2 Untreated common dendritic cell progenitor (CDP) - CDP_0h_1 - CDP_0h_2 TGF-beta1 treated (4 hours) CDP - CDP_4h_1 - CDP_4h_2 TGF-beta1 treated (8 hours) CDP - CDP_8h_1 - CDP_8h_2 TGF-beta1 treated (12 hours) CDP - CDP_12h_1 - CDP_12h_2 TGF-beta1 treated (24 hours) CDP - CDP_24h_1 - CDP_24h_2

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

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