1168 Neutrophil cytokines and NETs mediate skin and kidney inflammation in lupus flare under UVB irradiation

Ultraviolet B (UVB) triggers lupus flare by worsening skin lesions and systemic symptoms, i.e. nephritis. We have reported that UVB exposure induces inflammation with neutrophil infiltration extracellular trap (NET) formation in mice. also found induced proteinuria young female lupus-prone The relevant mechanisms regarding dermal-renal crosstalk is unclear. examined lesions, proteinuria, of neutrophils, their expression cytokines or complement C3, NETosis kidneys UVB-irradiated MRL/lpr inflammatory responses elevated thickness, immune cell infiltration, increased NETosis, deposition NET-associated IFNα C3 both kidneys. Infiltrated cells are positively correlated (r=0.57, p<0.05), suggesting a link between infiltrates kidney injury. In kidneys, glomerular hypercellularity, CXCR4-positive NETs, deposition, vitro, platelet-activating factor upregulated mouse portion them coexpress CXCR4, which may be mediator for transmigration Intraperitoneal application CXCR4 inhibitor IT1t significantly attenuated reduced neutrophils (3.2% vs 0.43% Area IT1t+UVB mice, P<0.01) Furthermore, overexpression nuclear lamin MRL/lpr-lmnb1Tg (r=0.49, p<0.01) (r=0.38, p<0.05) were proteinuria. Thus, inhibition CXCR4-mediated ameliorated UVB-triggered