NADPH oxidase in B cells and macrophages protects against murine lupus by regulation of TLR7

• DOI: 10.1172/jci.insight.178563
• Publication Date: 2024-07-23T17:50:21Z
• Authors: Rachael A. Gordon; Haylee A. Cosgrove; Anthony Marinov; Sebastien Gingras; Jeremy S. Tilstra; Allison M. Campbell; Sheldon I. Bastacky; Michael Kashgarian; Andras Perl; Kevin M. Nickerson; Mark J. Shlomchik
• Keywords: TLR7

Loss of NADPH oxidase (NOX2) exacerbates systemic lupus erythematosus (SLE) in mice and humans, but the mechanisms underlying this effect remain unclear. To identify cell lineages which NOX2 deficiency drives SLE, we employed conditional KO chimeric approaches to delete Cybb several hematopoietic MRL.Faslpr SLE-prone mice. Deletion macrophages/monocytes exacerbated SLE nephritis, though not degree observed global KOs. Unexpectedly, absence B cells resulted profound glomerulonephritis interstitial rivaling that seen with deletion. Furthermore, identified is a key regulator TLR7, driver pathology, both globally specifically cells. This mediated part through suppression TLR7-mediated NF-κB signaling Thus, NOX2's immunomodulatory orchestrated only by its function myeloid compartment, pivotal role selectively inhibiting TLR7 signaling.