Zinc finger transcription factor zDC is a negative regulator required to prevent activation of classical dendritic cells in the steady state

Meredith, M.M. et al. (2012) Zinc finger transcription factor zDC is a negative regulator required to prevent activation of classical dendritic cells in the steady state. Journal of Experimental Medicine, 209(9), pp. 1583-1593. (doi:10.1084/jem.20121003) (PMID:22851594) (PMCID:PMC3428942))

[img]
Preview
Text
110411.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial Share Alike.

2MB

Abstract

Classical dendritic cells (cDCs) process and present antigens to T cells. Under steady-state conditions, antigen presentation by cDCs induces tolerance. In contrast, during infection or inflammation, cDCs become activated, express higher levels of cell surface MHC molecules, and induce strong adaptive immune responses. We recently identified a cDC-restricted zinc finger transcription factor, zDC (also known as Zbtb46 or Btbd4), that is not expressed by other immune cell populations, including plasmacytoid DCs, monocytes, or macrophages. We define the zDC consensus DNA binding motif and the genes regulated by zDC using chromatin immunoprecipitation and deep sequencing. By deleting zDC from the mouse genome, we show that zDC is primarily a negative regulator of cDC gene expression. zDC deficiency alters the cDC subset composition in the spleen in favor of CD8+ DCs, up-regulates activation pathways in steady-state cDCs, including elevated MHC II expression, and enhances cDC production of vascular endothelial growth factor leading to increased vascularization of skin-draining lymph nodes. Consistent with these observations, zDC protein expression is rapidly down-regulated after TLR stimulation. Thus, zDC is a TLR-responsive, cDC-specific transcriptional repressor that is in part responsible for preventing cDC maturation in the steady state.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rihn, Dr Suzannah
Authors: Meredith, M.M., Liu, K., Kamphorst, A.O., Idoyaga, J., Yamane, A., Guermonprez, P., Rihn, S., Yao, K.-h., Silva, I.T., Oliveira, T.Y., Skokos, D., Casellas, R., and Nussenzweig, M.C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Experimental Medicine
Publisher:Rockefeller University Press
ISSN:0022-1007
ISSN (Online):1540-9538
First Published:First published in Journal of Experimental Medicine 209(9): 1583-1593
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record