{
  "abstract": "Introduction Systemic sclerosis (SSc) is characterized by tissue fibrosis, defined as excessive extracellular matrix (ECM) accumulation causing organ dysfunction. In SSc, ECM production is thought to be initiated by inflammatory triggers secondary to vascular injury. However, fibrosis seems to persist and progress even after inflammation resolves, suggesting an asynchrony between the resolution of inflammation and fibrosis. This study aims to characterize the evolution of fibrosis after the resolution of inflammation, using a prolonged experimental model of SSc.Material and Methods Experimental SSc was induced by daily hypochlorous acid (HOCl) injections into the backs of mice for 9 weeks. Mice (n= 12/group) were randomized in: i) mice receiving HOCl or PBS (control) for 42 days (D42); ii) mice receiving HOCl or PBS for 63 days (D63) and; iii) mice receiving HOCl or PBS for 42 days and sacrificed after 21 days without treatment (D42+21). Skin architecture and ECM accumulation were assessed histologically. Skin inflammatory cells and myofibroblasts were evaluated by immunohistochemical and immunofluorescence with anti-CD45 and α-SMA antibodies, respectively. Skin molecular programs were evaluated by RT-qPCR using a 22-gene panel of representative inflammatory and fibrotic markers.Results Compared with controls, D42 and D63 mice showed progressive dermal thickening, increased collagen deposition, and dermal adipocyte loss. Three weeks after stopping hocl injections, no significant decrease in dermal thickness or collagen accumulation was observed in the d42+21 group compared with d42 ( figure 1a). However, the alterations in cutaneous tissue architecture observed in the d42 and d63 groups regressed in the d42+21 group, with reappearance of adipocytes (figure 1b and c).Inflammatory cell infiltration regressed after HOCl discontinuation (figure 1d), consistent with a significant reduction in the expression of inflammatory cytokine genes (Ccl2, Cxcl1, Il6 and Il1b) (figure 2A). At d42+21, a significant modification of the ecm component gene expression profile was noted (decrease in col1a1 expression and increase in col7a1 expression, figure 2B). The balance between metalloproteinases and their inhibitors remained shifted toward ECM preservation (increased Timp1/Mmp3 ratio, figure 2C). A drop in the expression of myofibroblast differentiation genes was also observed (figure 2A) and reduced α-sma staining corroborated the decline in myofibroblast populations (figure 2D).Conclusions After cessation of the inflammatory trigger, inflammation regressed quickly and progressive ECM remodeling was observed, though without a return to baseline. These findings may help elucidate inflammation and fibrosis resolution mechanisms in SSc and guide the optimal timing for evaluating anti-inflammatory and anti-fibrotic therapies.Abstract P.031 Figure 1Abstract P.031 Figure 2",
  "authors": [
    {
      "affiliations": [
        "Univ. Lille, Inserm, CHU Lille, U1286 INFINITE Institute for Translational Research in Inflammation, Lille, France"
      ],
      "name": "Aurore Collet"
    },
    {
      "affiliations": [
        "Univ. Lille, Inserm, CHU Lille, U1286 INFINITE Institute for Translational Research in Inflammation, Lille, France"
      ],
      "name": "Manel Jendoubi"
    },
    {
      "affiliations": [
        "Univ. Lille, Inserm, CHU Lille, U1286 INFINITE Institute for Translational Research in Inflammation, Lille, France"
      ],
      "name": "Thomas Guerrier"
    },
    {
      "affiliations": [
        "Univ. Lille, Inserm, CHU Lille, U1286 INFINITE Institute for Translational Research in Inflammation, Lille, France"
      ],
      "name": "Alexis Largy"
    },
    {
      "affiliations": [
        "Univ. Lille, Inserm, CHU Lille, U1286 INFINITE Institute for Translational Research in Inflammation, Lille, France"
      ],
      "name": "Farah Mana"
    },
    {
      "affiliations": [
        "Univ. Lille, Inserm, CHU Lille, U1286 INFINITE Institute for Translational Research in Inflammation, Lille, France"
      ],
      "name": "Silvia Speca"
    },
    {
      "affiliations": [
        "Univ. Lille, Inserm, CHU Lille, U1286 INFINITE Institute for Translational Research in Inflammation, Lille, France"
      ],
      "name": "Sylvain Dubucquoi"
    },
    {
      "affiliations": [
        "Univ. Lille, Inserm, CHU Lille, U1286 INFINITE Institute for Translational Research in Inflammation, Lille, France"
      ],
      "name": "David Launay"
    }
  ],
  "title": "P.031 Distinct temporal dynamics of inflammation and fibrosis in a prolonged experimental model of systemic sclerosis",
  "uid": "e46f5b85-7e2b-5053-bd07-6deabcc263bb"
}