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Publication : pDC-like cells are pre-DC2 and require KLF4 to control homeostatic CD4 T cells.

First Author  Rodrigues PF Year  2023
Journal  Sci Immunol Volume  8
Issue  80 Pages  eadd4132
PubMed ID  36827419 Mgi Jnum  J:339120
Mgi Id  MGI:7517263 Doi  10.1126/sciimmunol.add4132
Citation  Rodrigues PF, et al. (2023) pDC-like cells are pre-DC2 and require KLF4 to control homeostatic CD4 T cells. Sci Immunol 8(80):eadd4132
abstractText  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 (T(H)17) 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 T(H)17 cells within skin-draining lymph nodes.
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