Abstract
Psoriasis is a chronic, inflammatory skin disease caused by a combination of environmental and genetic factors. The Tnip1 gene encodes A20 binding and inhibitor of NF-κB-1 (ABIN-1) protein and is strongly associated with susceptibility to psoriasis in humans. ABIN-1, a widely expressed ubiquitin-binding protein, restricts TNF- and TLR-induced signals. In this study, we report that mice lacking ABIN-1 specifically in dendritic cells (DCs), ABIN-1fl CD11c-Cre mice, exhibit perturbed immune homeostasis. ABIN-1–deficient DCs display exaggerated NF-κB and MAPK signaling and produce more IL-23 than do normal cells in response to TLR ligands. Challenge of ABIN-1fl CD11c-Cre mice with topical TLR7 ligand leads to greater numbers of Th17 and TCRγδ T cells and exacerbated development of psoriaform lesions. These phenotypes are reversed by DC-specific deletion of the TLR adaptor MyD88. These studies link ABIN-1 with IL-23 and IL-17, and they provide cellular and molecular mechanisms by which ABIN-1 regulates susceptibility to psoriasis.
Footnotes
This work was supported by grants from the National Institutes of Health (to A.M.) and by the Histopathology and Immunology Cores of the University of California, San Francisco Liver Center. G.E.H. was supported by National Institutes of Health Grant T32 DK007007. J.A.C. was partially supported by a National Science Foundation predoctoral fellowship.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- ABIN-1
- A20 binding and inhibitor of NF-κB-1
- BMDC
- bone marrow–derived dendritic cell
- cDC
- conventional dendritic cell
- DC
- dendritic cell
- IMQ
- imiquimod
- pDC
- plasmacytoid dendritic cell.
- Received December 14, 2012.
- Accepted May 13, 2013.
- Copyright © 2013 by The American Association of Immunologists, Inc.
In this issue
