Central Role of Dendritic Cells in Pulmonary Arterial Hypertension in Human and Mice
In: International journal of molecular sciences, Jg. 22 (2021-01-12), Heft 4
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Zugriff:
The pathogenesis of idiopathic pulmonary arterial hypertension (IPAH) is not fully understood, but evidence is accumulating that immune dysfunction plays a significant role. We previously reported that 31-week-old Tnfaip3DNGR1-KO mice develop pulmonary hypertension (PH) symptoms. These mice harbor a targeted deletion of the TNFα-induced protein-3 (Tnfaip3) gene, encoding the NF-κB regulatory protein A20, specifically in type I conventional dendritic cells (cDC1s). Here, we studied the involvement of dendritic cells (DCs) in PH in more detail. We found various immune cells, including DCs, in the hearts of Tnfaip3DNGR1-KO mice, particularly in the right ventricle (RV). Secondly, in young Tnfaip3DNGR1-KO mice, innate immune activation through airway exposure to toll-like receptor ligands essentially did not result in elevated RV pressures, although we did observe significant RV hypertrophy. Thirdly, PH symptoms in Tnfaip3DNGR1-KO mice were not enhanced by concomitant mutation of bone morphogenetic protein receptor type 2 (Bmpr2), which is the most affected gene in PAH patients. Finally, in human IPAH lung tissue we found co-localization of DCs and CD8+ T cells, representing the main cell type activated by cDC1s. Taken together, these findings support a unique role of cDC1s in PAH pathogenesis, independent of general immune activation or a mutation in the Bmpr2 gene.
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Central Role of Dendritic Cells in Pulmonary Arterial Hypertension in Human and Mice
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Autor/in / Beteiligte Person: | Boomars, K. A. ; Perros, Frédéric ; Ghigna, Maria-Rosa ; Gootjes, Chelsea ; Hendriks, Rudi W. ; Montani, David ; Geert van Loo ; Denise van Uden ; Koudstaal, Thomas ; Kool, Mirjam ; Thierry P P van den Bosch ; Morrell, Nicholas W. ; Jan H. von der Thüsen ; Jennifer A C van Hulst ; Bergen, Ingrid M. ; von der Thüsen, Jan H [0000-0001-9699-4860] ; van den Bosch, Thierry PP [0000-0002-7223-4565] ; Perros, Frédéric [0000-0001-7730-2427] ; Montani, David [0000-0002-9358-6922] ; Boomars, Karin A [0000-0003-1519-8147] ; Apollo - University of Cambridge Repository ; Medicine, Pulmonary ; Pathology ; von der Thüsen, Jan H. [0000-0001-9699-4860] ; van den Bosch, Thierry P. P. [0000-0002-7223-4565] ; Boomars, Karin A. [0000-0003-1519-8147] |
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Zeitschrift: | International journal of molecular sciences, Jg. 22 (2021-01-12), Heft 4 |
Veröffentlichung: | 2021 |
Medientyp: | unknown |
ISSN: | 1422-0067 (print) |
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