American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 2022
Impairment of the NKT-STAT1-CXCL9-axis Contributes to Vessel Fibrosis in Pulmonary Hypertension Due to Lung Fibrosis.
Rationale: Pulmonary hypertension (PH) is a common, severe comorbidity in interstitial lung diseases such as pulmonary fibrosis (PF), and it has limited treatment options. Excessive vascular fibrosis and inflammation are often present in PH, but the underlying mechanisms are still not well understood. Objectives: To identify a novel functional link between natural killer T (NKT) cell activation and vascular fibrosis in PF-PH. ⋯ Secretome analysis of peripheral blood mononuclear cells identified CXCL9 and CXCL10 as indicators of NKT cell activation. Pharmacologically, CXCL9, but not CXCL10, potently inhibited collagen deposition in hPASMCs via the chemokine receptor CXCR3. Conclusions: Our results indicate that the absence of NKT cells impairs the STAT1-CXCL9-CXCR3 axis in PF-PH and that restoration of this axis by NKT cell activation may unravel a novel therapeutic strategy to target vascular fibrosis in interstitial lung disease.
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Am. J. Respir. Crit. Care Med. · Oct 2022
Editorial CommentInsights into Endotheliopathy in COVID-19.