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Article Dans Une Revue Arthritis Research & Therapy Année : 2018

T-cell costimulation blockade is effective in experimental digestive and lung tissue fibrosis

Résumé

Background: We aimed to investigate the efficacy of abatacept in preclinical mouse models of digestive involvement, pulmonary fibrosis, and related pulmonary hypertension (PH), mimicking internal organ involvement in systemic sclerosis (SSc). Methods: Abatacept has been evaluated in the chronic graft-versus-host disease (cGvHD) mouse model (abatacept 1 mg/mL for 6 weeks), characterized by liver and intestinal fibrosis and in the Fra-2 mouse model (1 mg/mL or 10 mg/ mL for 4 weeks), characterized by interstitial lung disease (ILD) and pulmonary vascular remodeling leading to PH. Results: In the cGvHD model, abatacept significantly decreased liver transaminase levels and markedly improved colon inflammation. In the Fra-2 model, abatacept alleviated ILD, with a significant reduction in lung density on chest microcomputed tomography (CT), fibrosis histological score, and lung biochemical markers. Moreover, abatacept reversed PH in Fra-2 mice by improving vessel remodeling and related cardiac hemodynamic impairment. Abatacept significantly reduced fibrogenic marker levels, T-cell proliferation, and M1/M2 macrophage infiltration in lesional lungs of Fra-2 mice. Conclusion: Abatacept improves digestive involvement, prevents lung fibrosis, and attenuates PH. These findings suggest that abatacept might be an appealing therapeutic approach beyond skin fibrosis for organ involvement in SSc.
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hal-03828440 , version 1 (25-10-2022)

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Gonçalo Boleto, Christophe Guignabert, Sonia Pezet, Anne Cauvet, Jérémy Sadoine, et al.. T-cell costimulation blockade is effective in experimental digestive and lung tissue fibrosis. Arthritis Research & Therapy, 2018, 20 (1), pp.197. ⟨10.1186/s13075-018-1694-9⟩. ⟨hal-03828440⟩
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