Self-reactive IgE exacerbates interferon responses associated with autoimmunity

被引：136

作者：

Henault, Jill ^{[1
]}

Riggs, Jeffrey M. ^{[1
]}

Karnell, Jodi L. ^{[1
]}

Liarski, Vladimir M. ^{[2
,3
]}

Li, Jianqing ^{[1
]}

Shirinian, Lena ^{[4
]}

Xu, Linda ^{[4
]}

Casey, Kerry A. ^{[1
]}

Smith, Michael A. ^{[1
]}

Khatry, Deepak B. ^{[1
]}

Izhak, Liat ^{[1
]}

Clarke, Lorraine ^{[4
]}

Herbst, Ronald ^{[1
]}

Ettinger, Rachel ^{[1
]}

Petri, Michelle ^{[5
]}

Clark, Marcus R. ^{[2
,3
]}

Mustelin, Tomas ^{[1
]}

Kolbeck, Roland ^{[1
]}

Sanjuan, Miguel A. ^{[1
]}

机构：

[1] Medimmune Inc, Res Dept, Gaithersburg, MD 20878 USA

[2] Univ Chicago, Sect Rheumatol, Chicago, IL 60637 USA

[3] Univ Chicago, Gwen Knapp Ctr Lupus & Immunol Res, Chicago, IL 60637 USA

[4] Medimmune Inc, Antibody Discovery & Prot Engn Dept, Gaithersburg, MD 20878 USA

[5] Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD USA

来源：

NATURE IMMUNOLOGY | 2016年 / 17卷 / 02期

基金：

美国国家卫生研究院;

关键词：

PLASMACYTOID DENDRITIC CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; DISEASE-ACTIVITY; TRANSCRIPTION FACTORS; I INTERFERON; ANTIBODIES; NEPHRITIS; CHILDREN; RECEPTOR; ANTIGENS;

D O I：

10.1038/ni.3326

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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 Fc epsilon RI 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.

引用

页码：196 / 203

页数：8

共 42 条

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