Severe tissue trauma triggers the autoimmune state systemic lupus erythematosus in the MRL/++ lupus-prone mouse

K. Anam, M. Amare, S. Naik, K. A. Szabo, Thomas A. Davis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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/-Faslpr 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-1β, IL-6, TNF-α and PGE2 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.

Original languageEnglish
Pages (from-to)318-331
Number of pages14
Issue number4
StatePublished - 2009


  • Autoimmunity
  • Burns
  • Lupus
  • SLE
  • Trauma


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