International journal of molecular sciences, 2021-02, Vol.22 (4), p.1756
2021
Details
- Autor(en) / Beteiligte
- Titel
- Central Role of Dendritic Cells in Pulmonary Arterial Hypertension in Human and Mice
- Ist Teil von
- International journal of molecular sciences, 2021-02, Vol.22 (4), p.1756
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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 mice develop pulmonary hypertension (PH) symptoms. These mice harbor a targeted deletion of the TNFα-induced protein-3 ( ) 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 mice, particularly in the right ventricle (RV). Secondly, in young 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 mice were not enhanced by concomitant mutation of bone morphogenetic protein receptor type 2 ( ), 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 gene.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms22041756Titel-ID: cdi_doaj_primary_oai_doaj_org_article_3882264e6cd9454587529c7110bc26f7
- Format
- –
- Schlagworte
- A20 protein, Age, Animals, Antigens, BMPR2, Bone morphogenetic protein receptor type II, Bone Morphogenetic Protein Receptors, Type II - genetics, CD8 antigen, Chemokines, Cytokines, Dendritic cells, Dendritic Cells - immunology, Dendritic Cells - pathology, Dendritic structure, Familial Primary Pulmonary Hypertension - genetics, Familial Primary Pulmonary Hypertension - immunology, Familial Primary Pulmonary Hypertension - pathology, Gene Deletion, Genotype & phenotype, Heart Ventricles - immunology, Heart Ventricles - pathology, Humans, Hypertension, Hypertrophy, Immune system, Immunity, Innate, Immunology, inflammation, Life Sciences, Ligands, Localization, Lymphocytes, Lymphocytes T, Mice, Mutation, NF-κB protein, Pathogenesis, Proteins, pulmonary arterial hypertension, Pulmonary arteries, Pulmonary hypertension, Rodents, Tnfaip3, Toll-like receptor, Toll-Like Receptor 4 - immunology, Toll-like receptors, Tumor Necrosis Factor alpha-Induced Protein 3 - genetics, Tumor necrosis factor-α, Ventricle