Severe tissue trauma triggers the autoimmune state systemic lupus erythematosus in the MRL/++ lupus-prone mouse.
Tissue damage associated with a severe injury can result in profound inflammatory responses that may trigger autoimmune development in lupus-prone individuals. In this study, we investigated the role of a large full-thickness cutaneous burn injury on the early onset of autoimmune disease in lupus-prone MRL/++ mice. MRL/++ mice (chronic model) exhibit autoimmune symptoms at >70 weeks of age, whereas MRL/-Fas(lpr) mice (acute model) develop autoimmune disease in 17-22 weeks due to a lymphoproliferative mutation. Autoimmune disease developed in MRL/++ mice (4-15 weeks post injury) is manifested by skin lesions, vasculitis, epidermal ulcers, cellular infiltration, splenomegaly, lymphadenopathy, hypergammaglobulinemia, elevated autoantibodies and renal pathologies including proteinuria, glomerulonephritis and immune complex deposition; complications that contribute to reduced survival. Transcription studies of wound margin tissue show a correlation between the pathogenic effects of dysregulated IL-1beta, IL-6, TNF-alpha and PGE(2) synthesis during early wound healing and early onset of autoimmune disease. Interestingly, MRL/++ mice with healed wounds (30-40 days post burn) strongly rejected skin isografts. Conversely, skin isografts transplanted onto naive age-matched MRL/++ littermates achieved long-term survival. Collectively, these findings suggest that traumatic injury exacerbates inflammatory skin disease and severe multi-organ pathogenesis in lupus-prone mice.
Anam
K
K
Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, Maryland, USA.
Amare
M
M
Naik
S
S
Szabo
K A
KA
Davis
T A
TA
D000208:Acute Disease; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D002056:Burns / Q000276:immunology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D009154:Mutation; D015996:Survival Rate; D013997:Time Factors; D014945:Wound Healing / Q000276:immunology*