RT Journal Article
SR Electronic
T1 Cutting Edge: ABIN-1 Protects against Psoriasis by Restricting MyD88 Signals in Dendritic Cells
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 535
OP 539
DO 10.4049/jimmunol.1203335
VO 191
IS 2
A1 Callahan, Joseph A.
A1 Hammer, Gianna E.
A1 Agelides, Alexander
A1 Duong, Bao H.
A1 Oshima, Shigeru
A1 North, Jeffrey
A1 Advincula, Rommel
A1 Shifrin, Nataliya
A1 Truong, Hong-An
A1 Paw, Jonathan
A1 Barrera, Julio
A1 DeFranco, Anthony
A1 Rosenblum, Michael D.
A1 Malynn, Barbara A.
A1 Ma, Averil
YR 2013
UL http://www.jimmunol.org/content/191/2/535.abstract
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.