{
  "abstract": "Introduction The bleomycin-induced scleroderma model is a well-established and reliable method for generating a mouse model of systemic sclerosis (SSc). In the field of skin connective tissue diseases, accumulating evidence from both clinical and animal studies suggests that Toll-like receptors (TLRs) play a crucial role in various pathological processes.Material and Methods This study aimed to elucidate the roles of Toll-like receptor 7 (TLR7) and Toll-like receptor 9 (TLR9) in the immune dysregulation and fibrotic mechanisms associated with SSc. TLR7-knockout (TLR7-KO) and TLR9-knockout (TLR9-KO) mice, both on a BALB/c background, along with wild-type (WT) BALB/c mice, were used. All three strains were subjected to bleomycin (BLM) to induce scleroderma as the experimental groups, while WT mice treated with phosphate-buffered saline (PBS) served as controls.To evaluate the fibrotic and immunological phenotypes, we performed flow cytometry, reverse transcription–polymerase chain reaction (RT-PCR), histological analysis, and immunohistochemistry (IHC). In the SSc mouse model, TLR7 deficiency attenuated skin and lung fibrosis, whereas TLR9 deficiency exacerbated these fibrotic changes.Results TLR7 deletion led to a relative reduction in the infiltration and expression of pro-inflammatory and fibrotic cells and cytokines in the skin. In contrast, TLR9 deletion resulted in a relative increase in the infiltration of inflammatory and anti-inflammatory cells, as well as cytokines, suggesting a complex immunoregulatory role.Under the influence of plasmacytoid dendritic cells (pDCs), immune cell subset balances—including Beff/Breg (IL-6+ CD19+B cells / IL-10+CD19+B cells), Th17/Treg (IL-17A+CD4+T cells / Foxp3+CD25+CD4+ T cells), M1/M2 (CD86+/ CD206+ macrophages), and Th1/Th2 (TNFa+CD3+CD4+T cells / IL-4+CD3+CD4+T cells)—shifted toward an anti-inflammatory and anti-fibrotic profile with TLR7 deletion. Conversely, TLR9 deletion promoted a pro-inflammatory and pro-fibrotic shift in these immune balances.Conclusions Overall, TLR7 contributes to the progression of inflammation and fibrosis in the SSc model, whereas TLR9 appears to exert a protective effect. These findings indicate that TLR7 and TLR9 have opposing roles in the pathogenesis of SSc, influencing immune dysregulation and cutaneous fibrosis in divergent ways.",
  "authors": [
    {
      "affiliations": [
        "Kanazawa University, Kanazawa, Japan"
      ],
      "name": "Takashi Matsushita"
    },
    {
      "affiliations": [
        "Kanazawa University, Kanazawa, Japan"
      ],
      "name": "Chenyang Wang"
    },
    {
      "affiliations": [
        "Kanazawa University, Kanazawa, Japan"
      ],
      "name": "Yasuhito Hamaguc"
    }
  ],
  "title": "P.052 The role of TLR7 and TLR9 in the pathogenesis of systemic sclerosis",
  "uid": "448dcd7d-57ab-5ac3-8427-ccc9125e08bb"
}