PT  - JOURNAL ARTICLE
AU  - Matthieu Ponsoye
AU  - Camelia Frantz
AU  - Nadira Ruzehaji
AU  - Carole Nicco
AU  - Muriel Elhai
AU  - Barbara Ruiz
AU  - Anne Cauvet
AU  - Sonia Pezet
AU  - Marie Laure Brandely
AU  - Frédéric Batteux
AU  - Yannick Allanore
AU  - Jérôme Avouac
TI  - Treatment with abatacept prevents experimental dermal fibrosis and induces regression of established inflammation-driven fibrosis
AID  - 10.1136/annrheumdis-2015-208213
DP  - 2016 Dec 01
TA  - Annals of the Rheumatic Diseases
PG  - 2142--2149
VI  - 75
IP  - 12
4099  - http://ard.bmj.com/content/75/12/2142.short
4100  - http://ard.bmj.com/content/75/12/2142.full
SO  - Ann Rheum Dis2016 Dec 01; 75
AB  - Objective Activated T cells are the main component of the inflammatory skin infiltrates that characterise systemic sclerosis (SSc). Our aim was to investigate the efficacy of abatacept, which tempers T-cell activation, in reducing skin fibrosis in complementary mouse models of SSc.Methods The antifibrotic properties of abatacept were evaluated in the mouse models of bleomycin-induced dermal fibrosis and sclerodermatous chronic graft-versus-host disease, reflecting early and inflammatory stages of SSc. Thereafter, we studied the efficacy of abatacept in tight skin (Tsk-1) mice, an inflammation-independent mouse model of skin fibrosis.Results Abatacept efficiently prevented bleomycin-induced skin fibrosis and was also effective in the treatment of established fibrosis. In this model, abatacept decreased total and activated T-cell, B-cell and monocyte infiltration in the lesional skin. Abatacept did not protect CB17-SCID mice from the development of bleomycin-induced dermal fibrosis, which supports that T cells are necessary to drive the antifibrotic effects of abatacept. Upon bleomycin injections, skin interleukin (IL) 6 and IL-10 levels were significantly reduced upon abatacept treatment. Moreover, treatment with abatacept ameliorated fibrosis in the chronic graft-versus-host disease model, but demonstrated no efficacy in Tsk-1 mice. The tolerance of abatacept was excellent in the three mouse models.Conclusions Using complementary models, we demonstrate that inhibition of T-cell activation by abatacept can prevent and induce the regression of inflammation-driven dermal fibrosis. Translation to human disease is now required, and targeting early and inflammatory stages of SSc sounds the most appropriate for positioning abatacept in SSc.