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Isolevuglandins disrupt PU.1-mediated C1q expression and promote autoimmunity and hypertension in systemic lupus erythematosus

David M. Patrick, Néstor de la Visitación, Jaya Krishnan, Wei Chen, Michelle J. Ormseth, C. Michael Stein, Sean S. Davies, Venkataraman Amarnath, Leslie J. Crofford, Jonathan M. Williams, Shilin Zhao, Charles D. Smart, Sergey Dikalov, Anna Dikalova, Liang Xiao, Justin P. Van Beusecum, Mingfang Ao, Agnes B. Fogo, Annet Kirabo, and David G. Harrison

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Published August 17, 2022 - More info

Published in Volume 7, Issue 15 on August 8, 2022
JCI Insight. 2022;7(15):e163757. https://doi.org/10.1172/jci.insight.163757.
© 2022 expression et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published August 17, 2022 - Version history
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Isolevuglandins disrupt PU.1-mediated C1q expression and promote autoimmunity and hypertension in systemic lupus erythematosus
David M. Patrick, … , Annet Kirabo, David G. Harrison
David M. Patrick, … , Annet Kirabo, David G. Harrison
Research Article Inflammation

Isolevuglandins disrupt PU.1-mediated C1q expression and promote autoimmunity and hypertension in systemic lupus erythematosus

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Abstract

We describe a mechanism responsible for systemic lupus erythematosus (SLE). In humans with SLE and in 2 SLE murine models, there was marked enrichment of isolevuglandin-adducted proteins (isoLG adducts) in monocytes and dendritic cells. We found that antibodies formed against isoLG adducts in both SLE-prone mice and humans with SLE. In addition, isoLG ligation of the transcription factor PU.1 at a critical DNA binding site markedly reduced transcription of all C1q subunits. Treatment of SLE-prone mice with the specific isoLG scavenger 2-hydroxybenzylamine (2-HOBA) ameliorated parameters of autoimmunity, including plasma cell expansion, circulating IgG levels, and anti-dsDNA antibody titers. 2-HOBA also lowered blood pressure, attenuated renal injury, and reduced inflammatory gene expression uniquely in C1q-expressing dendritic cells. Thus, isoLG adducts play an essential role in the genesis and maintenance of systemic autoimmunity and hypertension in SLE.

Authors

David M. Patrick, Néstor de la Visitación, Jaya Krishnan, Wei Chen, Michelle J. Ormseth, C. Michael Stein, Sean S. Davies, Venkataraman Amarnath, Leslie J. Crofford, Jonathan M. Williams, Shilin Zhao, Charles D. Smart, Sergey Dikalov, Anna Dikalova, Liang Xiao, Justin P. Van Beusecum, Mingfang Ao, Agnes B. Fogo, Annet Kirabo, David G. Harrison

×

Original citation: JCI Insight. 2022;7(13):e136678. https://doi.org/10.1172/jci.insight.136678

Citation for this erratum: JCI Insight. 2022;7(15):e163757. https://doi.org/10.1172/jci.insight.163757

During the preparation of this manuscript, Figure 12 was inadvertently replaced with an incorrect figure. The correct Figure 12 is below. The article has also been corrected online.

Figure 12

The JCI regrets the error.

Footnotes

See the related article at Isolevuglandins disrupt PU.1 mediated C1q expression and promote autoimmunity and hypertension in systemic lupus erythematosus.

Version history
  • Version 1 (August 17, 2022): Electronic publication
  • Version 2 (September 29, 2022): Figure was added

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