title: Epidermal injury promotes nephritis flare in lupus-prone mice.
abstract: Systemic lupus erythematosus is clinically characterized by episodes of flare and remission. In patients, cutaneous exposure to ultraviolet light has been proposed as a flare trigger. However, induction of flare secondary to cutaneous exposure has been difficult to emulate in many murine lupus models. Here, we describe a system in which epidermal injury is able to trigger the development of a lupus nephritis flare in New Zealand Mixed (NZM) 2328 mice. 20-week old NZM2328 female mice underwent removal of the stratum corneum via duct tape, which resulted in rapid onset of proteinuria and death when compared to sham-stripped littermate control NZM2328 mice. This was coupled with a drop in serum C3 concentrations and dsDNA antibody levels and enhanced immune complex deposition in the glomeruli. Recruitment of CD11b(+)CD11c(+)F4/80(high) macrophages and CD11b(+)CD11c(+)F4/80(low) dendritic cells was noted prior to the onset of proteinuria in injured mice. Transcriptional changes within the kidney suggest a burst of type I IFN-mediated and inflammatory signaling which is followed by upregulation of CXCL13 following epidermal injury. Thus, we propose that tape stripping of lupus-prone NZM2328 mice is a novel model of lupus flare induction that will allow for the study of the role of cutaneous inflammation in lupus development and how crosstalk between dermal and systemic immune systems can lead to lupus flare.
authors: Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors: Kaitlyn L
authors: KL
authors: Clark
authors: Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors: Tamra J
authors: TJ
authors: Reed
authors: University of Michigan Program in Biomedical Sciences, University of Michigan, Ann Arbor, MI, USA.
authors: Sonya J
authors: SJ
authors: Wolf
authors: Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Department Dermatology, University of Michigan, Ann Arbor, MI, USA.
authors: Lori
authors: L
authors: Lowe
authors: Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors: Jeffrey B
authors: JB
authors: Hodgin
authors: Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. Electronic address: mkahlenb@med.umich.edu.
authors: J Michelle
authors: JM
authors: Kahlenberg
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000378:metabolism; D054382:Chemokine CXCL13 / Q000378:metabolism; D003176:Complement C3 / Q000032:analysis / Q000378:metabolism; D004247:DNA / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D004817:Epidermis / Q000276:immunology / Q000293:injuries*; D005260:Female; D007678:Kidney Glomerulus / Q000276:immunology* / Q000378:metabolism; D008181:Lupus Nephritis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011507:Proteinuria / Q000209:etiology / Q000276:immunology; D000067251:Symptom Flare Up
chemical_list: D000974:Antibodies, Antinuclear; C545610:C3 protein, mouse; D054382:Chemokine CXCL13; D003176:Complement C3; C486386:Cxcl13 protein, mouse; D004247:DNA
keywords: Chemokines; Flare; Lupus; Nephritis; Skin