| First Author | Callahan JA | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 2 | Pages | 535-9 |
| PubMed ID | 23785118 | Mgi Jnum | J:205446 |
| Mgi Id | MGI:5544877 | Doi | 10.4049/jimmunol.1203335 |
| Citation | Callahan JA, et al. (2013) Cutting edge: ABIN-1 protects against psoriasis by restricting MyD88 signals in dendritic cells. J Immunol 191(2):535-9 |
| abstractText | 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-kappaB-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-kappaB 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 TCRgammadelta 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. |
