Send to

Choose Destination
Ann Rheum Dis. 2016 Dec;75(12):2142-2149. doi: 10.1136/annrheumdis-2015-208213. Epub 2016 Feb 24.

Treatment with abatacept prevents experimental dermal fibrosis and induces regression of established inflammation-driven fibrosis.

Author information

Université Paris Descartes, Sorbonne Paris Cité, INSERM U1016 and CNRS UMR8104, Institut Cochin, Paris, France.
Service de Pharmacie Clinique, GH Hôpitaux Universitaires Paris Centre, Hôpital Cochin, Paris, France.
Laboratoire d'Immunologie biologique, Hôpital Cochin, AP-HP, Paris, France.
Université Paris Descartes, Sorbonne Paris Cité, Service de Rhumatologie A, Hôpital Cochin, Paris, France.



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.


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.


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.


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.


Inflammation; Systemic Sclerosis; T Cells

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center