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

Abstract:

: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.

journal_name

Lupus

journal_title

Lupus

authors

Anam K,Amare M,Naik S,Szabo KA,Davis TA

doi

10.1177/0961203308097479

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

318-31

issue

4

eissn

0961-2033

issn

1477-0962

pii

18/4/318

journal_volume

18

pub_type

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