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

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.

SUBMITTER: Patrick DM

PROVIDER: S-EPMC9310530 | biostudies-literature |

REPOSITORIES: biostudies-literature

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

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

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Isolevuglandins modify immune function in hypertension in systemic lupus erythematosus

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Systemic lupus erythematosus

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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