title: Cutting edge: ABIN-1 protects against psoriasis by restricting MyD88 signals in dendritic cells.
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-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.
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Callahan
authors.forename: Gianna E
authors.initials: GE
authors.lastname: Hammer
authors.forename: Alexander
authors.initials: A
authors.lastname: Agelides
authors.forename: Bao H
authors.initials: BH
authors.lastname: Duong
authors.forename: Shigeru
authors.initials: S
authors.lastname: Oshima
authors.forename: Jeffrey
authors.initials: J
authors.lastname: North
authors.forename: Rommel
authors.initials: R
authors.lastname: Advincula
authors.forename: Nataliya
authors.initials: N
authors.lastname: Shifrin
authors.forename: Hong-An
authors.initials: HA
authors.lastname: Truong
authors.forename: Jonathan
authors.initials: J
authors.lastname: Paw
authors.forename: Julio
authors.initials: J
authors.lastname: Barrera
authors.forename: Anthony
authors.initials: A
authors.lastname: DeFranco
authors.forename: Michael D
authors.initials: MD
authors.lastname: Rosenblum
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Malynn
authors.forename: Averil
authors.initials: A
authors.lastname: Ma
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004198:Disease Susceptibility; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020381:Interleukin-17; D053759:Interleukin-23; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C477038:Tlr7 protein, mouse; C503281:Tnip2 protein, mouse; D051199:Toll-Like Receptor 7; D020928:Mitogen-Activated Protein Kinases