| First Author | Kass DJ | Year | 2012 |
| Journal | Am J Pathol | Volume | 180 |
| Issue | 5 | Pages | 1963-78 |
| PubMed ID | 22429962 | Mgi Jnum | J:183382 |
| Mgi Id | MGI:5318609 | Doi | 10.1016/j.ajpath.2012.01.010 |
| Citation | Kass DJ, et al. (2012) Cytokine-Like Factor 1 Gene Expression Is Enriched in Idiopathic Pulmonary Fibrosis and Drives the Accumulation of CD4(+) T Cells in Murine Lungs: Evidence for an Antifibrotic Role in Bleomycin Injury. Am J Pathol 180(5):1963-78 |
| abstractText | Idiopathic pulmonary fibrosis (IPF) is a progressive and typically fatal lung disease. To gain insight into the pathogenesis of IPF, we reanalyzed our previously published gene expression data profiling IPF lungs. Cytokine receptor-like factor 1 (CRLF1) was among the most highly up-regulated genes in IPF lungs, compared with normal controls. The protein product (CLF-1) and its partner, cardiotrophin-like cytokine (CLC), function as members of the interleukin 6 (IL-6) family of cytokines. Because of earlier work implicating IL-6 family members in IPF pathogenesis, we tested whether CLF-1 expression contributes to inflammation in experimental pulmonary fibrosis. In IPF, we detected CLF-1 expression in both type II alveolar epithelial cells and macrophages. We found that the receptor for CLF-1/CLC signaling, ciliary neurotrophic factor receptor (CNTFR), was expressed only in type II alveolar epithelial cells. Administration of CLF-1/CLC to both uninjured and bleomycin-injured mice led to the pulmonary accumulation of CD4(+) T cells. We also found that CLF-1/CLC administration increased inflammation but decreased pulmonary fibrosis. CLF-1/CLC leads to significantly enriched expression of T-cell-derived chemokines and cytokines, including the antifibrotic cytokine interferon-gamma. We propose that, in IPF, CLF-1 is a selective stimulus of type II alveolar epithelial cells and may potentially drive an antifibrotic response by augmenting both T-helper-1-driven and T-regulatory-cell-driven inflammatory responses in the lung. |
