PMID- 27527596
OWN - NLM
STAT- MEDLINE
DCOM- 20170808
LR  - 20180122
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 197
IP  - 6
DP  - 2016 Sep 15
TI  - Essential Requirement for IFN Regulatory Factor 7 in Autoantibody Production but 
      Not Development of Nephritis in Murine Lupus.
PG  - 2167-76
LID - 10.4049/jimmunol.1502445 [doi]
AB  - Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease
      characterized by the production of autoantibodies against nuclear components.
      Recent genetic studies of SLE patients have revealed that IFN regulatory factor
      (IRF) 7 gene polymorphisms are associated with an increased risk of SLE, but the 
      precise role of IRF7 in SLE development is not fully understood. We investigated 
      the role of IRF7 in the pathogenesis of SLE using a mouse model and saw a curious
      dissociation of autoantibody production and development of glomerulonephritis.
      SLE was chemically induced into IRF7-deficient mice, and glomerulonephritis with 
      deposits of IgG and lipogranulomas were observed after 10 mo. However, these mice
      failed to produce anti-dsDNA, ssDNA, ribonucleoprotein, and Sm autoantibodies.
      Following the chemical induction, IRF7-deficient mice expressed substantially
      lower levels of IFN-stimulated genes than did wild-type mice, but NF-kappaB
      target genes were equally upregulated in both strains. Therefore, the type I IFN 
      pathway seems critical for the autoantibody production, but the NF-kappaB
      activation is sufficient for the development of glomerulonephritis in this model.
      Our study thus demonstrates a specific requirement for IRF7 in autoantibody
      production and uncovers a new layer of complexity in the pathogenesis of SLE.
CI  - Copyright (c) 2016 by The American Association of Immunologists, Inc.
FAU - Miyagawa, Fumi
AU  - Miyagawa F
AD  - Department of Dermatology, Nara Medical University School of Medicine, Kashihara,
      Nara 634-8522, Japan; fumim@naramed-u.ac.jp.
FAU - Tagaya, Yutaka
AU  - Tagaya Y
AUID- ORCID: 0000-0002-1342-9282
AD  - Institute of Human Virology, University of Maryland School of Medicine,
      Baltimore, MD 21201; and.
FAU - Ozato, Keiko
AU  - Ozato K
AUID- ORCID: 0000-0001-7013-2728
AD  - Laboratory of Molecular Growth Regulation, National Institute of Child Health and
      Human Development, National Institutes of Health, Bethesda, MD 20892.
FAU - Asada, Hideo
AU  - Asada H
AUID- ORCID: 0000-0003-1971-9835
AD  - Department of Dermatology, Nara Medical University School of Medicine, Kashihara,
      Nara 634-8522, Japan;
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160815
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (1-(3-picolinium)-12-triethylammonium-dodecane dibromide)
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Autoantibodies)
RN  - 0 (Interferon Regulatory Factor-7)
RN  - 0 (Irf7 protein, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (Picolines)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Antibodies, Antinuclear/biosynthesis
MH  - Apoptosis/drug effects
MH  - Autoantibodies/*biosynthesis
MH  - Dendritic Cells/physiology
MH  - Female
MH  - Glomerulonephritis/etiology
MH  - Interferon Regulatory Factor-7/*physiology
MH  - Lupus Nephritis/*etiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/physiology
MH  - Neutrophils/physiology
MH  - Picolines/pharmacology
EDAT- 2016/08/17 06:00
MHDA- 2017/08/09 06:00
CRDT- 2016/08/17 06:00
PHST- 2015/11/20 00:00 [received]
PHST- 2016/07/13 00:00 [accepted]
PHST- 2016/08/17 06:00 [entrez]
PHST- 2016/08/17 06:00 [pubmed]
PHST- 2017/08/09 06:00 [medline]
AID - jimmunol.1502445 [pii]
AID - 10.4049/jimmunol.1502445 [doi]
PST - ppublish
SO  - J Immunol. 2016 Sep 15;197(6):2167-76. doi: 10.4049/jimmunol.1502445. Epub 2016
      Aug 15.