PMID- 26692173
OWN - NLM
STAT- MEDLINE
DCOM- 20160606
LR  - 20220330
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Print)
IS  - 1529-2908 (Linking)
VI  - 17
IP  - 2
DP  - 2016 Feb
TI  - Self-reactive IgE exacerbates interferon responses associated with autoimmunity.
PG  - 196-203
LID - 10.1038/ni.3326 [doi]
AB  - Canonically, immunoglobulin E (IgE) mediates allergic immune responses by 
      triggering mast cells and basophils to release histamine and type 2 helper 
      cytokines. Here we found that in human systemic lupus erythematosus (SLE), IgE 
      antibodies specific for double-stranded DNA (dsDNA) activated plasmacytoid 
      dendritic cells (pDCs), a type of cell of the immune system linked to viral 
      defense, which led to the secretion of substantial amounts of interferon-alpha 
      (IFN-alpha). The concentration of dsDNA-specific IgE found in patient serum 
      correlated with disease severity and greatly potentiated pDC function by 
      triggering phagocytosis via the high-affinity FcvarepsilonRI receptor for IgE, followed by 
      Toll-like receptor 9 (TLR9)-mediated sensing of DNA in phagosomes. Our findings 
      expand the known pathogenic mechanisms of IgE-mediated inflammation beyond those 
      found in allergy and demonstrate that IgE can trigger interferon responses 
      capable of exacerbating self-destructive autoimmune responses.
FAU - Henault, Jill
AU  - Henault J
AD  - Research Department, MedImmune, Gaithersburg, Maryland, USA.
FAU - Riggs, Jeffrey M
AU  - Riggs JM
AD  - Research Department, MedImmune, Gaithersburg, Maryland, USA.
FAU - Karnell, Jodi L
AU  - Karnell JL
AD  - Research Department, MedImmune, Gaithersburg, Maryland, USA.
FAU - Liarski, Vladimir M
AU  - Liarski VM
AD  - Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, 
      University of Chicago, Chicago, Illinois, USA.
FAU - Li, Jianqing
AU  - Li J
AD  - Research Department, MedImmune, Gaithersburg, Maryland, USA.
FAU - Shirinian, Lena
AU  - Shirinian L
AD  - Antibody Discovery and Protein Engineering Department, MedImmune, Gaithersburg, 
      Maryland, USA.
FAU - Xu, Linda
AU  - Xu L
AD  - Antibody Discovery and Protein Engineering Department, MedImmune, Gaithersburg, 
      Maryland, USA.
FAU - Casey, Kerry A
AU  - Casey KA
AD  - Research Department, MedImmune, Gaithersburg, Maryland, USA.
FAU - Smith, Michael A
AU  - Smith MA
AD  - Research Department, MedImmune, Gaithersburg, Maryland, USA.
FAU - Khatry, Deepak B
AU  - Khatry DB
AD  - Research Department, MedImmune, Gaithersburg, Maryland, USA.
FAU - Izhak, Liat
AU  - Izhak L
AD  - Research Department, MedImmune, Gaithersburg, Maryland, USA.
FAU - Clarke, Lorraine
AU  - Clarke L
AD  - Antibody Discovery and Protein Engineering Department, MedImmune, Gaithersburg, 
      Maryland, USA.
FAU - Herbst, Ronald
AU  - Herbst R
AD  - Research Department, MedImmune, Gaithersburg, Maryland, USA.
FAU - Ettinger, Rachel
AU  - Ettinger R
AD  - Research Department, MedImmune, Gaithersburg, Maryland, USA.
FAU - Petri, Michelle
AU  - Petri M
AD  - Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Clark, Marcus R
AU  - Clark MR
AD  - Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, 
      University of Chicago, Chicago, Illinois, USA.
FAU - Mustelin, Tomas
AU  - Mustelin T
AD  - Research Department, MedImmune, Gaithersburg, Maryland, USA.
FAU - Kolbeck, Roland
AU  - Kolbeck R
AD  - Research Department, MedImmune, Gaithersburg, Maryland, USA.
FAU - Sanjuan, Miguel A
AU  - Sanjuan MA
AD  - Research Department, MedImmune, Gaithersburg, Maryland, USA.
LA  - eng
GR  - R01 AR043727/AR/NIAMS NIH HHS/United States
GR  - R01 AR055646/AR/NIAMS NIH HHS/United States
GR  - U19 AI082724/AI/NIAID NIH HHS/United States
GR  - AR-43727/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20151221
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Autoantibodies)
RN  - 0 (Cytokines)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Toll-Like Receptor 9)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9008-11-1 (Interferons)
SB  - IM
CIN - Cell Res. 2016 Mar;26(3):271-2. PMID: 26794873
MH  - Antibodies, Antinuclear/immunology
MH  - Antigen-Antibody Complex/immunology/metabolism
MH  - Autoantibodies/*immunology
MH  - *Autoimmunity
MH  - B-Lymphocytes/immunology/metabolism
MH  - Cytokines/blood/metabolism
MH  - Dendritic Cells/immunology/metabolism
MH  - Female
MH  - Humans
MH  - Immunoglobulin E/blood/*immunology
MH  - Immunoglobulin G/blood/immunology
MH  - Interferons/*metabolism
MH  - Leukocytes, Mononuclear/immunology/metabolism
MH  - Lupus Erythematosus, Systemic/blood/immunology/metabolism
MH  - Lupus Nephritis/immunology/pathology
MH  - Male
MH  - Phagocytosis/immunology
MH  - Phagosomes/metabolism
MH  - Plasma Cells/immunology/metabolism
MH  - Toll-Like Receptor 9/metabolism
PMC - PMC4718782
MID - NIHMS731890
EDAT- 2015/12/23 06:00
MHDA- 2016/06/09 06:00
PMCR- 2016/06/21
CRDT- 2015/12/23 06:00
PHST- 2015/08/25 00:00 [received]
PHST- 2015/10/19 00:00 [accepted]
PHST- 2015/12/23 06:00 [entrez]
PHST- 2015/12/23 06:00 [pubmed]
PHST- 2016/06/09 06:00 [medline]
PHST- 2016/06/21 00:00 [pmc-release]
AID - ni.3326 [pii]
AID - 10.1038/ni.3326 [doi]
PST - ppublish
SO  - Nat Immunol. 2016 Feb;17(2):196-203. doi: 10.1038/ni.3326. Epub 2015 Dec 21.