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P074 Il-10 regulates skin thickness and scaling in imiquimod-induced psoriasis-like skin inflammation in mice
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  1. X Xu1,
  2. E Prens1,
  3. E Florencia1,
  4. L Boon2,
  5. P Asmawidjaja1,
  6. A-M Otten-Mus1,
  7. E Lubberts1
  1. 1Erasmus MC Rotterdam, Rotterdam
  2. 2Bioceros, Utrecht, Netherlands

Abstract

Introduction Psoriasis is an autoimmune skin disease affecting around 0.6% to 3% of the whole population with detrimental physical and societal impacts. Previously, we established a psoriasis-like skin inflammation model in mice using topical application of imiquimod (IMQ). This model successfully re-captures all critical features of clinical psoriasis such as keratinocyte hyperproliferation, munro’s microabscesses, and shares a similar infiltration profile of various immune cells. Previous data suggest up-regulation of IL-10, but its role in this psoriasiform model is not clear.

Objectives To investigate the role of IL-10 in the IMQ-induced psoriasis-like skin inflammation.

Methods Psoriasis-like skin inflammation was induced by topical application of imiquimod (Aldara) for 5 or 10 days. Mice were injected intraperitoneally with anti-IL-10 or an isotype control antibody or subcutaneously with dexamethasone. Back skin of mice was scored for up to 10 days using a modified Psoriasis Area and Severity Index (PASI) score system adapted from clinical PASI score. Inflammation and skin thickness were scored histologically. Gene expression and immune cells in the skin were analysed using RT-PCR and flow cytometry, respectively.

Results At day 10, both skin thickness and scaling score were significantly higher after neutralising IL-10 compared to isotype control, or either group compared to dexamethasone-treated animals. At days 5 and 10, H and E staining confirmed that epidermal thickness was more prominent in anti-IL-10 treated mice compared to isotype control or dexamethasone-treated mice, with more profound differences at day 10. Ki-67 staining for proliferating keratinocytes showed more proliferation at the epidermal basal layer after neutralising IL-10. In addition, significant more infiltration of neutrophils was found in skin at day 10. At day 5, IL-23/IL-17 pathway cytokines were more significantly upregulated in anti-IL-10 group than the isotype control group, while at day 10, a significant upregulation of IL-19, IL-24 expression were found in anti-IL-10 group compared to isotype control.

Conclusions IL-10 regulates skin thickness and scaling during psoriasis-like skin inflammation. Furthermore, our data suggested that IL-10 might influence psoriatic symptoms through dampening of IL-23/IL-17 axis in early phase (day 5) and reducing IL-19 and IL-24 expression at late stage (day 10). The negative feedback signal of IL-10 partially explains the observed decrease of inflammation in imiquimod-induced skin inflammation after day 5.

Disclosure of interest X. Xu: None declared, E. Prens: None declared, E. Florencia: None declared, L. Boon: None declared, P. Asmawidjaja: None declared, A.-M. Otten-Mus: None declared, E. Lubberts Grant/research support from: Novartis

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