| Autor: |
Habiel, David M., Espindola, Milena S., Kitson, Chris, Azzara, Anthony V., Coelho, Ana Lucia, Stripp, Barry, Hogaboam, Cory M. |
| Zdroj: |
Mucosal immunology; January 2019, Vol. 12 Issue: 1 p212-222, 11p |
| Abstrakt: |
Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease, with unknown etiopathogenesis and suboptimal therapeutic options. Previous reports have shown that increased T-cell numbers and CD28nullphenotype is predictive of prognosis in IPF, suggesting that these cells might have a role in this disease. Flow cytometric analysis of explanted lung cellular suspensions showed a significant increase in CD8+CD28nullT cells in IPF relative to normal lung explants. Transcriptomic analysis of CD3+T cells isolated from IPF lung explants revealed a loss of CD28-transcript expression and elevation of pro-inflammatory cytokine expression in IPF relative to normal T cells. IPF lung explant-derived T cells (enriched with CD28nullT cells), but not normal donor lung CD28+T cells induced dexamethasone-resistant lung remodeling in humanized NSG mice. Finally, CD28nullT cells expressed similar CTLA4 and significantly higher levels of PD-1 proteins relative to CD28+T cells and blockade of either proteins in humanized NSG mice, using anti-CTLA4, or anti-PD1, mAb treatment-accelerated lung fibrosis. Together, these results demonstrate that IPF CD28nullT cells may promote lung fibrosis but the immune checkpoint proteins, CTLA-4 and PD-1, appears to limit this effect. |
| Databáze: |
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