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Abstract: FR-PO594

CD11b Activation Suppresses suPAR and Inflammatory Signaling to Ameliorate Lupus Nephritis in Murine Models

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation


  • Villanueva, Veronica, Rush University Medical Center, Chicago, Illinois, United States
  • Li, Xiaobo, Rush University Medical Center, Chicago, Illinois, United States
  • Khan, Samia Qamar, Editas Medicine, Cambridge, Massachusetts, United States
  • Jimenez, Viviana, Rush University Medical Center, Chicago, Illinois, United States
  • Altintas, Mehmet M., Rush University Medical Center, Chicago, Illinois, United States
  • Faridi, Hafeez, Chicago State University College of Pharmacy, Chicago, Illinois, United States
  • Reiser, Jochen, Rush University Medical Center, Chicago, Illinois, United States
  • Niewold, Timothy B., Hospital for Special Surgery Department of Medicine, New York, New York, United States
  • Gupta, Vineet, Rush University Medical Center, Chicago, Illinois, United States

Lupus nephritis (LN) is a debilitating comorbidity of systemic lupus erythematosus (SLE). CD11b, the alpha-chain of integrin dimer CD11b/CD18, is highly expressed on myeloid cells and plays a critical role in their adhesion, migration, and signaling. Single nucleotide polymorphisms (SNPs) in the ITGAM gene, encoding CD11b, are significantly associated with LN and reduce integrin function. Additionally, levels of pro-inflammatory mediators, such as suPAR, are increased in the LN sera. We previously described CD11b activation using novel agonist LA1 as a novel modulator of integrin function. Here we investigated how CD11b-dependent signaling modulates such pro-inflammatory molecules.


We used a combination of in vitro and in vivo assays. We utilized macrophage cell lines and primary macrophages. Cells were treated with TLR agonists, pathway inhibitors, and CD11b agonist leukadherin-1 (LA1). Changes in protein expression were assessed by western blot and proinflammatory cytokine levels were assessed by ELISA. For complementary in vivo studies, we utilized wild type, CD11b knockout (KO) and a CD11b knockin (KI) expressing a constitutively activating mutation. We induced SLE and LN in these models and studied the efficacy of genetic and pharmacologic CD11b activation as a therapeutic strategy.


TLR-stimulation increased inflammation and suPAR levels in vitro. Importantly, CD11b activation significantly reduced proinflammatory cytokines and suPAR, suggesting a novel mechanism for controlling inflammation in glomerular diseases. Mechanistically, CD11b activation reduced TLR-dependent activation of NFkB and NLRP3/Caspase-1 pathways. In vivo, CD11b activation significantly reduced levels of suPAR and proteinuria.


We demonstrate that CD11b activation reduced myeloid cell generated suPAR in models of lupus and lupus nephritis. These studies provide further support for CD11b activation as a therapeutic strategy for autoimmune diseases.


  • NIDDK Support