Interleukin-6/interleukin-21 signaling axis is critical in the pathogenesis of pulmonary arterial hypertension
Copyright policy )Interleukin-6/interleukin-21 signaling axis is critical in the pathogenesis of pulmonary arterial hypertension
Significance Pulmonary arterial hypertension (PAH) is a serious disease characterized by vascular remodeling in pulmonary arteries. Although an elevated IL-6 serum level correlates with poor prognosis of PAH patients, it is unclear how IL-6 promotes PAH. Here we identified IL-21 as a downstream target of IL-6 signaling in PAH. In mice with hypoxia-induced pulmonary hypertension (HPH), Th17 cells and M2 macrophages accumulate in the lungs after hypoxia exposure. IL-21 primarily derived from Th17 cells promotes M2 macrophage polarization. Consistently, IL-21 receptor-deficient mice show resistance to HPH with no accumulation of M2 macrophages in the lungs. IL-21 and M2 macrophage markers were upregulated in the lungs of patients with end-stage idiopathic PAH. These findings suggest promising therapeutic strategies for PAH targeting IL-6/IL-21–signaling axis.
- University of Tokyo Japan
- Hokkaido Bunkyo University Japan
- Hokkaido University Japan
- Osaka University Japan
- Japan Science and Technology Agency Japan
Male, Mice, Knockout, Analysis of Variance, Interleukin-6, Hypertension, Pulmonary, Interleukins, Macrophages, Blotting, Western, Antibodies, Monoclonal, Blood Pressure, Flow Cytometry, Real-Time Polymerase Chain Reaction, Immunohistochemistry, Mice, Inbred C57BL, Mice, Animals, Humans, Body Weights and Measures, Receptors, Interleukin-21, DNA Primers
Male, Mice, Knockout, Analysis of Variance, Interleukin-6, Hypertension, Pulmonary, Interleukins, Macrophages, Blotting, Western, Antibodies, Monoclonal, Blood Pressure, Flow Cytometry, Real-Time Polymerase Chain Reaction, Immunohistochemistry, Mice, Inbred C57BL, Mice, Animals, Humans, Body Weights and Measures, Receptors, Interleukin-21, DNA Primers
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