Cutting edge: ABIN-1 protects against psoriasis by restricting MyD88 signals in dendritic cells.

Journal Article (Journal Article)

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-1(fl) 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-1(fl) 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.

Full Text

Duke Authors

Cited Authors

  • Callahan, JA; Hammer, GE; Agelides, A; Duong, BH; Oshima, S; North, J; Advincula, R; Shifrin, N; Truong, H-A; Paw, J; Barrera, J; DeFranco, A; Rosenblum, MD; Malynn, BA; Ma, A

Published Date

  • July 15, 2013

Published In

Volume / Issue

  • 191 / 2

Start / End Page

  • 535 - 539

PubMed ID

  • 23785118

Pubmed Central ID

  • PMC3702626

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1203335


  • eng

Conference Location

  • United States