| First Author | Vander Lugt B | Year | 2017 |
| Journal | J Cell Biol | Volume | 216 |
| Issue | 3 | Pages | 779-792 |
| PubMed ID | 28130292 | Mgi Jnum | J:250366 |
| Mgi Id | MGI:5920868 | Doi | 10.1083/jcb.201512012 |
| Citation | Vander Lugt B, et al. (2017) Transcriptional determinants of tolerogenic and immunogenic states during dendritic cell maturation. J Cell Biol 216(3):779-792 |
| abstractText | Dendritic cells (DCs) promote either tolerogenic or immunogenic T cell responses, the latter upon sensing microbes. Using an in vitro system, we analyzed transcriptional determinants that enable mature DCs to direct these opposing T cell outcomes. In the absence of microbial products, the transcription factor interferon regulatory factor 4 (IRF4) promotes regulatory T cell (Treg) generation by enhancing expression of genes required for antigen presentation along with those for T cell tolerance. IRF4-deficient DCs were impaired for Treg generation in vivo. When exposed to microbial stimuli, DCs activated nuclear factor (NF)-kappaB, which induced expression of a proinflammatory cytokine module that, along with the antigen presentation module, promoted the generation of effector T cells. NF-kappaB was, however, dispensable for Treg development. Chromatin profiling revealed transcriptional motifs associated with the divergent DC programs. Thus, DCs modulate their ability to prime tolerogenic or immunogenic T cells by expressing a core antigen presentation module that is overlaid by distinctive regulatory modules to promote either tolerance or immunity. |
