Self-reactive IgE exacerbates interferon responses associated with autoimmunity

Jill Henault; Jeffrey M. Riggs; Jodi L. Karnell; Vladimir M. Liarski; Jianqing Li; Lena Shirinian; Linda Xu; Kerry A. Casey; Michael A. Smith; Deepak B. Khatry; Liat Izhak; Lorraine Clarke; Ronald Herbst; Rachel Ettinger; Michelle Petri; Marcus R. Clark; Tomas Mustelin; Roland Kolbeck; Miguel A. Sanjuan

doi:10.1038/ni.3326

Self-reactive IgE exacerbates interferon responses associated with autoimmunity

Jill Henault, Jeffrey M. Riggs, Jodi L. Karnell, Vladimir M. Liarski, Jianqing Li, Lena Shirinian, Linda Xu, Kerry A. Casey, Michael A. Smith, Deepak B. Khatry, Liat Izhak, Lorraine Clarke, Ronald Herbst, Rachel Ettinger, Michelle Petri, Marcus R. Clark, Tomas Mustelin, Roland Kolbeck, Miguel A. Sanjuan

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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-α (IFN-α). 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 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.

Original language	English (US)
Pages (from-to)	196-203
Number of pages	8
Journal	Nature Immunology
Volume	17
Issue number	2
DOIs	https://doi.org/10.1038/ni.3326
State	Published - Feb 1 2016

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Henault, J., Riggs, J. M., Karnell, J. L., Liarski, V. M., Li, J., Shirinian, L., Xu, L., Casey, K. A., Smith, M. A., Khatry, D. B., Izhak, L., Clarke, L., Herbst, R., Ettinger, R., Petri, M., Clark, M. R., Mustelin, T., Kolbeck, R., & Sanjuan, M. A. (2016). Self-reactive IgE exacerbates interferon responses associated with autoimmunity. Nature Immunology, 17(2), 196-203. https://doi.org/10.1038/ni.3326

Henault, J, Riggs, JM, Karnell, JL, Liarski, VM, Li, J, Shirinian, L, Xu, L, Casey, KA, Smith, MA, Khatry, DB, Izhak, L, Clarke, L, Herbst, R, Ettinger, R, Petri, M, Clark, MR, Mustelin, T, Kolbeck, R & Sanjuan, MA 2016, 'Self-reactive IgE exacerbates interferon responses associated with autoimmunity', Nature Immunology, vol. 17, no. 2, pp. 196-203. https://doi.org/10.1038/ni.3326

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title = "Self-reactive IgE exacerbates interferon responses associated with autoimmunity",

abstract = "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-α (IFN-α). 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 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.",

author = "Jill Henault and Riggs, {Jeffrey M.} and Karnell, {Jodi L.} and Liarski, {Vladimir M.} and Jianqing Li and Lena Shirinian and Linda Xu and Casey, {Kerry A.} and Smith, {Michael A.} and Khatry, {Deepak B.} and Liat Izhak and Lorraine Clarke and Ronald Herbst and Rachel Ettinger and Michelle Petri and Clark, {Marcus R.} and Tomas Mustelin and Roland Kolbeck and Sanjuan, {Miguel A.}",

note = "Funding Information: We thank S. Cohen (MedImmune) for antibody to IgE; M. Rebelatto, M. Czapiga, K. Dacosta, W. King and H. Koelkebeck for discussions; E. Grant and K. Stover for critical manuscript review; E. Grant and M. Parker and the Autoimmunity Molecular Medicine Group (Medimmune) for assistance with clinical samples; and K. Zerrouki for assistance with manuscript editing. Supported by the US National Institutes of Health (AR-43727).",

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doi = "10.1038/ni.3326",

language = "English (US)",

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AU - Henault, Jill

AU - Riggs, Jeffrey M.

AU - Karnell, Jodi L.

AU - Liarski, Vladimir M.

AU - Li, Jianqing

AU - Shirinian, Lena

AU - Xu, Linda

AU - Casey, Kerry A.

AU - Smith, Michael A.

AU - Khatry, Deepak B.

AU - Izhak, Liat

AU - Clarke, Lorraine

AU - Herbst, Ronald

AU - Ettinger, Rachel

AU - Petri, Michelle

AU - Clark, Marcus R.

AU - Mustelin, Tomas

AU - Kolbeck, Roland

AU - Sanjuan, Miguel A.

N1 - Funding Information: We thank S. Cohen (MedImmune) for antibody to IgE; M. Rebelatto, M. Czapiga, K. Dacosta, W. King and H. Koelkebeck for discussions; E. Grant and K. Stover for critical manuscript review; E. Grant and M. Parker and the Autoimmunity Molecular Medicine Group (Medimmune) for assistance with clinical samples; and K. Zerrouki for assistance with manuscript editing. Supported by the US National Institutes of Health (AR-43727).

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 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-α (IFN-α). 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 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.

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-α (IFN-α). 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 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.

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Self-reactive IgE exacerbates interferon responses associated with autoimmunity

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