Dendritic cells heterogeneity and function

National Institute Of Dental & Craniofacial Research

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Abstract

Our research has highlighted heterogeneity within plasmacytoid dendritic cells (pDCs) and has addressed functional specificity within subsets. pDCs have been shown to play an important role during immune responses, ranging from initial viral control through the production of type I interferons to antigen presentation. We identified a previously uncharacterized immune subset, referred to as pDC-like cells, that not only resembles pDCs but also shares conventional DC (cDC) features. We could show that this subset is a circulating precursor distinct from common DC progenitors, with prominent cDC2 potential. Our findings from human CD2-iCre and CD300c-iCre lineage tracing mouse models suggest that a substantial fraction of cDC2s originates from pDC-like cells, which can therefore be referred to as pre-DC2. This precursor subset responds to homeostatic cytokines, such as macrophage colony stimulating factor, by expanding and differentiating into cDC2 that efficiently prime T helper 17 (TH17) cells. Under homeostatic conditions, pre-DC2 develop into cDC2 cells that regulate the immune threshold at barrier sites by controlling the pool of TH17 cells within skin-draining lymph nodes. Th17 cells at barrier tissues control the integrity of epithelial cells but are also responsible in autoimmune conditions such as psoriasis. We will now dissect the mechanisms that will determine the balance between autoimmunity and maintenance of tissue integrity.