PT  - JOURNAL ARTICLE
AU  - Callahan, Joseph A.
AU  - Hammer, Gianna E.
AU  - Agelides, Alexander
AU  - Duong, Bao H.
AU  - Oshima, Shigeru
AU  - North, Jeffrey
AU  - Advincula, Rommel
AU  - Shifrin, Nataliya
AU  - Truong, Hong-An
AU  - Paw, Jonathan
AU  - Barrera, Julio
AU  - DeFranco, Anthony
AU  - Rosenblum, Michael D.
AU  - Malynn, Barbara A.
AU  - Ma, Averil
TI  - Cutting Edge: ABIN-1 Protects against Psoriasis by Restricting MyD88 Signals in Dendritic Cells
AID  - 10.4049/jimmunol.1203335
DP  - 2013 Jul 15
TA  - The Journal of Immunology
PG  - 535--539
VI  - 191
IP  - 2
4099  - http://www.jimmunol.org/content/191/2/535.short
4100  - http://www.jimmunol.org/content/191/2/535.full
SO  - J. Immunol.2013 Jul 15; 191
AB  - 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.