論文 - 詳細
| RRC ID | 89601 |
|---|---|
| 著者 | Evangelista JF, Nisperuza Vidal AK, Xu D, Islamuddin M, Chen Y, Wang C, Freitas R, Liu S, Engler-Chiurazzi E, Blair RV, Datta PK, Qin X. |
| タイトル | TLR7 signaling aggravates lung inflammation associated with increased anti-Scl-70 autoantibody production in murine bleomycin-induced systemic sclerosis. |
| ジャーナル | Front Immunol |
| Abstract |
OBJECTIVE:Systemic sclerosis (SSc) is a severe autoimmune disease characterized by immune dysregulation, fibrosis, and substantial morbidity and mortality. Although type I interferon-related pathways have been implicated in SSc, the contribution of Toll-like receptor 7 (TLR7) and its downstream signaling, including the transcription factor interferon regulatory factor 7 (IRF7) and effector molecules such as CCL2 and CCL12, to disease pathogenesis remains unclear. METHODS:We used a bleomycin (BLM)-induced mouse model of SSc. Male wild-type (WT), Tlr7-deficient (Tlr7-/- ), and Irf7-deficient (Irf7-/- ) mice (10-12 weeks old) received daily subcutaneous BLM (2.5 mg/kg/day) for 4 weeks. In a separate experiment, BLM-treated WT mice were treated with the CCR2 antagonist (RS504393). Disease features were evaluated by histopathology, ELISA, flow cytometry, western blotting, RT-qPCR, and Olink proteomics. RESULTS:BLM-treated Tlr7-/- and Irf7-/- mice showed less body weight loss, reduced pulmonary interstitial inflammation, fewer inflammatory monocytes in the spleen, lower pulmonary type I interferon-related gene expression, and lower serum anti-topoisomerase I autoantibody (anti-Scl-70) levels. Pharmacologic CCR2 antagonism attenuated BLM-induced body weight loss, lung injury, and reduced dermal collagen deposition. CONCLUSION:These findings support a pathogenic role for TLR7-IRF7-IFN-I signaling in anti-Scl-70 autoantibody production and pulmonary inflammation in experimental SSc, and suggest that downstream chemokine pathways may represent therapeutic targets. |
| 巻・号 | 17 |
| ページ | 1823229 |
| 公開日 | 2026-1-1 |
| DOI | 10.3389/fimmu.2026.1823229 |
| PMID | 42459669 |
| PMC | PMC13368542 |
| MeSH | Animals Autoantibodies* / immunology Bleomycin Chemokine CCL2 Disease Models, Animal Interferon Regulatory Factor-7 / genetics Interferon Regulatory Factor-7 / metabolism Male Membrane Glycoproteins* / genetics Membrane Glycoproteins* / immunology Membrane Glycoproteins* / metabolism Mice Mice, Inbred C57BL Mice, Knockout Scleroderma, Systemic* / chemically induced Scleroderma, Systemic* / immunology Scleroderma, Systemic* / metabolism Scleroderma, Systemic* / pathology Signal Transduction / immunology Toll-Like Receptor 7* / genetics Toll-Like Receptor 7* / immunology Toll-Like Receptor 7* / metabolism |
| リソース情報 | |
| 実験動物マウス | RBRC01420 |