Alternative activation of lung macrophages and the development of scleroderma-related lung fibrosis / Scleroderma Research Foundation Grant Program

Project: Research project

Project Details


Pulmonary fibrosis has emerged as the leading cause of death in patients with Systemic Sclerosis (SSc). Currently available therapies are only marginally effective in treating this devastating condition and even patients who respond to therapy are left with significant respiratory morbidity. Recent studies have identified, that pulmonary macrophages from patients with SSc display abnormal activation and exhibit profibrotic (also known as M2) phenotype, producing TGFb, matrix metalloproteinases and other profibrotic molecules. Most current therapies modulate the number or activity of bone marrow-derived myeloid cells, including macrophages. However, macrophages in the lung tend to be relatively resistant to these therapies, largely because they are long-lived and capable of maintaining their pool without input from the bone marrow. We hypothesize that prevention/suppression of profibrotic M2 activation of pulmonary macrophages in situ, rather than decreasing number of recruited bone marrow-derived myeloid cells, will have beneficial effect on the course of SSc-related pulmonary fibrosis. This hypothesis is especially attractive since it may allow us to target already established lung fibrosis. Moreover, if successful, this approach may be applicable to other forms of lung fibrosis. We will address this hypothesis using state of the art animal models, including novel humanize mouse model and bone marrow chimeras with thoracic shielding.
Effective start/end date12/15/1412/14/17


  • ATS Foundation Inc. and the Scleroderma Foundation, Inc. (Letter 12/09/2014)


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