التفاصيل البيبلوغرافية
| العنوان: |
Classical dendritic cells contribute to hypoxia‐induced pulmonary hypertension. |
| المؤلفون: |
Mickael, Claudia1,2 (AUTHOR) claudia.mickael@cuanschutz.edu, Sanders, Linda A.1,2 (AUTHOR), Lee, Michael H.3,4 (AUTHOR), Kumar, Rahul3,4 (AUTHOR), Fonseca‐Balladares, Dara3,4 (AUTHOR), Gandjeva, Aneta2 (AUTHOR), Cautivo‐Reyes, Kelly5,6 (AUTHOR), Kassa, Biruk3,4 (AUTHOR), Kumar, Sushil2 (AUTHOR), Irwin, David2 (AUTHOR), Swindle, Delaney2 (AUTHOR), Phang, Tzu7 (AUTHOR), Stearman, Robert S.8 (AUTHOR), Molofsky, Ari B.5 (AUTHOR), McKee, Amy S.9,10 (AUTHOR), Stenmark, Kurt R.2 (AUTHOR), Graham, Brian B.3,4 (AUTHOR), Tuder, Rubin M.1,2 (AUTHOR) |
| المصدر: |
FASEB Journal. 8/31/2024, Vol. 38 Issue 16, p1-20. 20p. |
| مستخلص: |
Pulmonary hypertension (PH) is a chronic and progressive disease with significant morbidity and mortality. It is characterized by remodeled pulmonary vessels associated with perivascular and intravascular accumulation of inflammatory cells. Although there is compelling evidence that bone marrow‐derived cells, such as macrophages and T cells, cluster in the vicinity of pulmonary vascular lesions in humans and contribute to PH development in different animal models, the role of dendritic cells in PH is less clear. Dendritic cells' involvement in PH is likely since they are responsible for coordinating innate and adaptive immune responses. We hypothesized that dendritic cells drive hypoxic PH. We demonstrate that a classical dendritic cell (cDC) subset (cDC2) is increased and activated in wild‐type mouse lungs after hypoxia exposure. We observe significant protection after the depletion of cDCs in ZBTB46 DTR chimera mice before hypoxia exposure and after established hypoxic PH. In addition, we find that cDC depletion is associated with a reduced number of two macrophage subsets in the lung (FolR2+ MHCII+ CCR2+ and FolR2+ MHCII+ CCR2−). We found that depleting cDC2s, but not cDC1s, was protective against hypoxic PH. Finally, proof‐of‐concept studies in human lungs show increased perivascular cDC2s in patients with Idiopathic Pulmonary Arterial Hypertension (IPAH). Our data points to an essential role of cDCs, particularly cDC2s, in the pathophysiology of experimental PH.Bone‐marrow‐derived immature classical dendritic cells, particularly cDC2s, are activated directly or indirectly by hypoxia, resulting in higher expression of cytokines, chemokines, and growth factors in the lung. Recruitment of monocytes and cDC2s from the circulation culminates in perivascular inflammation and hypoxia‐induced pulmonary hypertension. (Created with Biorender.com). [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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