التفاصيل البيبلوغرافية
| العنوان: |
Cytokine-Like Factor 1 Gene Expression Is Enriched in Idiopathic Pulmonary Fibrosis and Drives the Accumulation of CD4+T Cells in Murine Lungs |
| المؤلفون: |
Kass, Daniel J., Yu, Guoying, Loh, Katrina S., Savir, Asaf, Borczuk, Alain, Kahloon, Rehan, Juan-Guardela, Brenda, Deiuliis, Giuseppe, Tedrow, John, Choi, Jiin, Richards, Thomas, Kaminski, Naftali, Greenberg, Steven M. |
| المصدر: |
American Journal of Pathology; May 2012, Vol. 180 Issue: 5 p1963-1978, 16p |
| مستخلص: |
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-γ. 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. |
| قاعدة البيانات: |
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