| First Author | Miller HL | Year | 2021 |
| Journal | Proc Natl Acad Sci U S A | Volume | 118 |
| Issue | 3 | PubMed ID | 33431694 |
| Mgi Jnum | J:300758 | Mgi Id | MGI:6502722 |
| Doi | 10.1073/pnas.2021364118 | Citation | Miller HL, et al. (2021) Altered ratio of dendritic cell subsets in skin-draining lymph nodes promotes Th2-driven contact hypersensitivity. Proc Natl Acad Sci U S A 118(3):e2021364118 |
| abstractText | Plasmacytoid dendritic cells (pDCs) specialize in the production of type I IFN (IFN-I). pDCs can be depleted in vivo by injecting diphtheria toxin (DT) in a mouse in which pDCs express a diphtheria toxin receptor (DTR) transgene driven by the human CLEC4C promoter. This promoter is enriched for binding sites for TCF4, a transcription factor that promotes pDC differentiation and expression of pDC markers, including CLEC4C. Here, we found that injection of DT in CLEC4C-DTR(+) mice markedly augmented Th2-dependent skin inflammation in a model of contact hypersensitivity (CHS) induced by the hapten fluorescein isothiocyanate. Unexpectedly, this biased Th2 response was independent of reduced IFN-I accompanying pDC depletion. In fact, DT treatment altered the representation of conventional dendritic cells (cDCs) in the skin-draining lymph nodes during the sensitization phase of CHS; there were fewer Th1-priming CD326(+) CD103(+) cDC1 and more Th2-priming CD11b(+) cDC2. Single-cell RNA-sequencing of CLEC4C-DTR(+) cDCs revealed that CD326(+) DCs, like pDCs, expressed DTR and were depleted together with pDCs by DT treatment. Since CD326(+) DCs did not express Tcf4, DTR expression might be driven by yet-undefined transcription factors activating the CLEC4C promoter. These results demonstrate that altered DC representation in the skin-draining lymph nodes during sensitization to allergens can cause Th2-driven CHS. |
