PMID- 27807192
OWN - NLM
STAT- MEDLINE
DCOM- 20170726
LR  - 20180124
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 197
IP  - 11
DP  - 2016 Dec 1
TI  - Suppression of IRAK1 or IRAK4 Catalytic Activity, but Not Type 1 IFN Signaling,
      Prevents Lupus Nephritis in Mice Expressing a Ubiquitin Binding-Defective Mutant 
      of ABIN1.
PG  - 4266-4273
AB  - Polymorphisms in the TNIP1 gene encoding A20-binding inhibitor of NF-kappaB1
      (ABIN1) predispose to lupus and other autoimmune diseases in at least eight human
      populations. We found previously that knock-in mice expressing a
      ubiquitin-binding-defective mutant of ABIN1 (ABIN1[D485N]) develop autoimmunity
      as they age and succumb to a disease resembling lupus nephritis in humans. In
      this article, we report that Flt3-derived dendritic cells from these mice
      overproduced type 1 IFNs upon stimulation with ligands that activate TLR7 or
      TLR9. However, crossing ABIN1[D485N] mice to IFNAR1-knockout mice that do not
      express the alpha-subunit of the type 1 IFNR did not prevent splenomegaly, the
      appearance of high serum levels of autoantibodies and other Igs, or liver
      inflammation and only reduced kidney inflammation modestly. In contrast, crossing
      ABIN1[D485N] mice to knock-in mice expressing catalytically inactive mutants of
      IRAK1 or IRAK4 prevented splenomegaly, autoimmunity, and liver and kidney
      inflammation. Our results support the notion that IRAK1 and/or IRAK4 are
      attractive targets for the development of drugs to prevent, and perhaps treat,
      lupus nephritis and other autoinflammatory diseases caused by the decreased
      ability of ABIN1 or other proteins to restrict the strength of MyD88 signaling.
CI  - Copyright (c) 2016 The Authors.
FAU - Nanda, Sambit K
AU  - Nanda SK
AD  - Medical Research Council Protein Phosphorylation and Ubiquitylation Unit,
      University of Dundee, Dundee DD1 5EH, United Kingdom; s.k.nanda@dundee.ac.uk
      p.cohen@dundee.ac.uk.
FAU - Lopez-Pelaez, Marta
AU  - Lopez-Pelaez M
AD  - Medical Research Council Protein Phosphorylation and Ubiquitylation Unit,
      University of Dundee, Dundee DD1 5EH, United Kingdom.
FAU - Arthur, J Simon C
AU  - Arthur JS
AD  - Division of Immunology and Cell Signaling, School of Life Sciences, University of
      Dundee, Dundee DD1 5EH, United Kingdom; and.
FAU - Marchesi, Francesco
AU  - Marchesi F
AUID- ORCID: 0000-0003-1179-5788
AD  - School of Veterinary Medicine, University of Glasgow, Glasgow G61 1QH, United
      Kingdom.
FAU - Cohen, Philip
AU  - Cohen P
AD  - Medical Research Council Protein Phosphorylation and Ubiquitylation Unit,
      University of Dundee, Dundee DD1 5EH, United Kingdom; s.k.nanda@dundee.ac.uk
      p.cohen@dundee.ac.uk.
LA  - eng
GR  - MC_UU_12016/11/Medical Research Council/United Kingdom
GR  - MR/K000985/1/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161102
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Interferon Type I)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Tlr7 protein, mouse)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Tnip2 protein, mouse)
RN  - 0 (Toll-Like Receptor 7)
RN  - 0 (Toll-Like Receptor 9)
RN  - EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
RN  - EC 2.7.11.1 (Irak1 protein, mouse)
RN  - EC 2.7.11.1 (Irak4 protein, mouse)
SB  - AIM
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics/*immunology
MH  - Amino Acid Substitution
MH  - Animals
MH  - Crosses, Genetic
MH  - Gene Expression Regulation/genetics/*immunology
MH  - Gene Knock-In Techniques
MH  - Interferon Type I/genetics/*immunology
MH  - Interleukin-1 Receptor-Associated Kinases/genetics/*immunology
MH  - Kidney
MH  - Lupus Nephritis/genetics/*immunology/pathology/prevention & control
MH  - Membrane Glycoproteins/genetics/immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Mutation, Missense
MH  - Myeloid Differentiation Factor 88/genetics/immunology
MH  - Signal Transduction/genetics/immunology
MH  - Toll-Like Receptor 7/genetics/immunology
MH  - Toll-Like Receptor 9/genetics/immunology
PMC - PMC5114882
MID - EMS70167
EDAT- 2016/11/04 06:00
MHDA- 2017/07/27 06:00
CRDT- 2016/11/04 06:00
PHST- 2016/05/03 00:00 [received]
PHST- 2016/09/29 00:00 [accepted]
PHST- 2016/11/04 06:00 [pubmed]
PHST- 2017/07/27 06:00 [medline]
PHST- 2016/11/04 06:00 [entrez]
AID - jimmunol.1600788 [pii]
AID - 10.4049/jimmunol.1600788 [doi]
PST - ppublish
SO  - J Immunol. 2016 Dec 1;197(11):4266-4273. doi: 10.4049/jimmunol.1600788. Epub 2016
      Nov 2.