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