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NADPH oxidase in B cells and macrophages protects against murine lupus by regulation of TLR7.
- Source :
-
JCI insight [JCI Insight] 2024 Jul 23; Vol. 9 (16). Date of Electronic Publication: 2024 Jul 23. - Publication Year :
- 2024
-
Abstract
- Loss of NADPH oxidase (NOX2) exacerbates systemic lupus erythematosus (SLE) in mice and humans, but the mechanisms underlying this effect remain unclear. To identify the cell lineages in which NOX2 deficiency drives SLE, we employed conditional KO and chimeric approaches to delete Cybb in several hematopoietic cell lineages of MRL.Faslpr SLE-prone mice. Deletion of Cybb in macrophages/monocytes exacerbated SLE nephritis, though not to the degree observed in the Cybb global KOs. Unexpectedly, the absence of Cybb in B cells resulted in profound glomerulonephritis and interstitial nephritis, rivaling that seen with global deletion. Furthermore, we identified that NOX2 is a key regulator of TLR7, a driver of SLE pathology, both globally and specifically in B cells. This is mediated in part through suppression of TLR7-mediated NF-κB signaling in B cells. Thus, NOX2's immunomodulatory effect in SLE is orchestrated not only by its function in the myeloid compartment, but through a pivotal role in B cells by selectively inhibiting TLR7 signaling.
- Subjects :
- Animals
Mice
Signal Transduction
Female
Disease Models, Animal
NF-kappa B metabolism
Lupus Nephritis immunology
Lupus Nephritis pathology
Lupus Nephritis metabolism
Lupus Nephritis genetics
Membrane Glycoproteins
Toll-Like Receptor 7 metabolism
Toll-Like Receptor 7 genetics
B-Lymphocytes immunology
B-Lymphocytes metabolism
NADPH Oxidase 2 metabolism
NADPH Oxidase 2 genetics
Macrophages immunology
Macrophages metabolism
Lupus Erythematosus, Systemic immunology
Lupus Erythematosus, Systemic metabolism
Mice, Knockout
Subjects
Details
- Language :
- English
- ISSN :
- 2379-3708
- Volume :
- 9
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- JCI insight
- Publication Type :
- Academic Journal
- Accession number :
- 39042716
- Full Text :
- https://doi.org/10.1172/jci.insight.178563