Lung
fibrosis is characterized by abnormal accumulation of fibroblasts in the interstitium of the alveolar space. Two populations of myofibroblasts, distinguished by Thy1 expression, are detected in human and murine lungs. Accumulation of Thy1-negative (Thy1(-)) myofibroblasts was shown in the lungs of humans with
idiopathic pulmonary fibrosis (IPF) and of
bleomycin-treated mice. We aimed to identify genetic changes in lung myofibroblasts following Thy1 crosslinking and assess the impact of specific lung myofibroblast Thy1-deficiency, in vivo,
in bleomycin-injured mouse lungs. Thy1 increased in mouse lung lymphocytes following
bleomycin injury but decreased in myofibroblasts when
fibrosis was at the highest point (14 days), as assessed by immunohistochemistry. Using gene chip analysis, we detected that myofibroblast Thy1 crosslinking mediates downregulation of genes promoting cell proliferation, survival, and differentiation, and reduces production of extracellular matrix (ECM) components, while concurrently mediating the upregulation of genes known to foster
inflammation and immunological functions. Chimeric Thy1-deficient mice with Thy1(+) lymphocytes and Thy1(-) myofibroblasts showed
fibrosis similar to wild-type mice and an increased number of CD4/CD25 regulatory T cells, with a concomitant decrease in
inflammation. Lung myofibroblasts downregulate Thy1 expression to increase their proliferation but to diminish the in vivo inflammatory milieu.
Inflammation is not essential for evolution of
fibrosis as was previously stated.