Journal
SCIENCE IMMUNOLOGY
Volume 8, Issue 80, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.add4132
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Plasmacytoid dendritic cells (pDCs) play a critical role in immune responses, but recent studies have discovered a previously unknown immune subset called pDC-like cells. These cells not only resemble pDCs but also have features of conventional DCs (cDCs). It has been found that a significant proportion of cDC2s originate from these pDC-like cells, which can be referred to as pre-DC2. This precursor subset responds to homeostatic cytokines and differentiates into cDC2, which prime T helper 17 (TH17) cells. The development of pre-DC2 into specific cDC2 subsets requires the transcription factor KLF4 and plays a role in regulating immune responses at barrier sites.
Plasmacytoid dendritic cells (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. However, recent studies uncovered unexpected heterogeneity among pDCs. 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 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. Development of pre-DC2 into CX3CR1(+) ESAM(-) cDC2b but not CX3CR1(-) ESAM(+) cDC2a requires the transcription factor KLF4. Last, we show that, under homeostatic conditions, this developmental pathway regulates the immune threshold at barrier sites by controlling the pool of TH17 cells within skin-draining lymph nodes.
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