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THU0256 Complement C3 Exacerbates TLR7-Mediated Skin Inflammation but Not Systemic Autoimmunity
  1. C. Giacomassi,
  2. G.S. Ling,
  3. N. Buang,
  4. J. Strid,
  5. M. Botto
  1. Centre for Complement and Inflammation Research (CCIR), Department of Medicine, Imperial College, London, United Kingdom

Abstract

Background Short–term topical application of a Toll-like receptor 7 (TLR7) agonist, Imiquimod (IMQ), is a widely used murine model of psoriasis. Recently long–term epicutaneous application (4–8 weeks) of IMQ has been shown to elicit lupus-like manifestations. Importantly the topical application of IMQ induced more potent systemic effects than the intraperitoneal administration, indicating that activation of the TLR7-signalling in the skin plays a key role.

Objectives Since complement activation is known to have a crucial role in the regulation of local inflammation and in the pathogenesis of lupus, we investigated whether C3 played a role in the induction of the cutaneous lesions as well as in the lupus-like syndrome triggered by IMQ

Methods BALB/c wild-type (WT) and C3-deficient (BALB/c.C3–/–) mice were treated with topical application of 5% IMQ cream for either 7 consecutive days (short-term) or 3 days /week for 11 weeks (long-term).

Results After 7 days, skin thickening (ear thickness at day 7: WT 60.14 mm ± 1.625, n=7, vs BALB/c.C3–/– 50.88 mm ± 2.460, n=8, p value=0.0094) and local neutrophil recruitment (cell number at day 7: 52.3±6.736, n=7, vs BALB/c.C3–/– 30.33±4.192, n=7, p value=0.0170) were significantly reduced in the absence of C3. The expansion of IL17+ γδ+ T cells in the draining lymph nodes was also significantly impaired (day 7: WT 59.06% ± 2.961, n=7, vs BALB/c.C3–/– 46.21% ± 2.023, n=8, p value=0.0029). Long-term IMQ treatment resulted in the development of similar low titres of auto-antibodies in both groups of mice (anti-RNP: WT 29.75±11.33, n=5 vs BALB/c.C3–/– 97.28±41.53, n=5, p=0.1553; anti-ssDNA: WT 9.252±3.367, n=5, vs BALB/c.C3–/–20.70±12.03, n=5, p=0.386; anti-chromatin: WT 12.59±7.001, n=5, vs BALB/c.C3–/– 16.72±12.60, n=5, p=0.781). In addition, the kidney histology scored by a trained histopathologist evidenced no difference in the glomerulonephritis severity.

Conclusions Collectively, these data suggest that C3 acts as a potential mediator of IMQ-induced skin inflammation. However, the different local tissue response does not result in an altered autoimmune response in the C3-deficient mice. The study of the involvement of other complement components is currently in progress.

Disclosure of Interest None declared

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