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

Arthritis Research & Therapy
Gonçalo BoletoJérôme Avouac

Abstract

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). 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. 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. Abatacept improves digestive involvement, prevents lung fibrosis, and attenuates PH. These findings sugg...Continue Reading

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Mar 18, 2020·Expert Opinion on Investigational Drugs·Melody P Chung, Lorinda Chung
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Methods Mentioned

BETA
transgenic
biopsies
enzyme-linked immunosorbent assay
ELISA
flow cytometry

Clinical Trials Mentioned

NCT02161406

Software Mentioned

Ctan Brucker
Rigaku
ImageJ

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