Reference - Detail
| RRC ID | 76635 |
|---|---|
| Author | Kim S, Chen J, Jo S, Ou F, Ferris ST, Liu TT, Ohara RA, Anderson DA, Wu R, Chen MY, Gillanders WE, Gillanders WE, Murphy TL, Murphy KM. |
| Title | IL-6 selectively suppresses cDC1 specification via C/EBPβ. |
| Journal | J Exp Med |
| Abstract |
Cytokines produced in association with tumors can impair antitumor immune responses by reducing the abundance of type 1 conventional dendritic cells (cDC1), but the mechanism remains unclear. Here, we show that tumor-derived IL-6 generally reduces cDC development but selectively impairs cDC1 development in both murine and human systems through the induction of C/EBPβ in the common dendritic cell progenitor (CDP). C/EBPβ and NFIL3 compete for binding to sites in the Zeb2 -165 kb enhancer and support or repress Zeb2 expression, respectively. At homeostasis, pre-cDC1 specification occurs upon Nfil3 induction and consequent Zeb2 suppression. However, IL-6 strongly induces C/EBPβ expression in CDPs. Importantly, the ability of IL-6 to impair cDC development is dependent on the presence of C/EBPβ binding sites in the Zeb2 -165 kb enhancer, as this effect is lost in Δ1+2+3 mutant mice in which these binding sites are mutated. These results explain how tumor-associated IL-6 suppresses cDC1 development and suggest therapeutic approaches preventing abnormal C/EBPβ induction in CDPs may help reestablish cDC1 development to enhance antitumor immunity. |
| Volume | 220(10) |
| Published | 2023-10-2 |
| DOI | 10.1084/jem.20221757 |
| PII | 214227 |
| PMID | 37432392 |
| PMC | PMC10336151 |
| MeSH | Animals Binding Sites Cytokines* Dendritic Cells Homeostasis Humans Interleukin-6* Mice |
| IF | 11.743 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 48 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC09240 |