The inflammatory cell landscape in the lungs of patients with idiopathic pulmonary arterial hypertension

• Published in: The European respiratory journal Vol. 51; no. 1; p. 1701214
• Main Authors: Marsh, Leigh M, Jandl, Katharina, Grünig, Gabriele, Foris, Vasile, Bashir, Mina, Ghanim, Bahil, Klepetko, Walter, Olschewski, Horst, Olschewski, Andrea, Kwapiszewska, Grazyna
• Format: Journal Article
• Language: English
• Published: England European Respiratory Society Journals Ltd 01.01.2018; European Respiratory Society
• Subjects: Adaptive Immunity; Adult; Autoimmune diseases; Autoimmunity; CD11c antigen; CD123 antigen; CD14 antigen; CD3 antigen; CD4 antigen; CD45 antigen; CD8 antigen; Computational Biology; Computer applications; Computer Simulation; Dendritic cells; Dendritic Cells - cytology; Female; Flow Cytometry; Histocompatibility antigen HLA; Humans; Hypertension; Hypertension, Pulmonary - metabolism; Hypertension, Pulmonary - pathology; Immunophenotyping; Inflammation; Inflammation - metabolism; Inflammation - pathology; Intraepithelial Lymphocytes - cytology; Leukocyte Common Antigens - metabolism; Leukocytes (basophilic); Leukocytes (neutrophilic); Lung - metabolism; Lung - pathology; Lungs; Lymphocytes T; Male; Mast cells; Middle Aged; Original; Principal Component Analysis; Principal components analysis; Pulmonary Artery - pathology; Pulmonary hypertension
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/13993003.01214-2017

Increasing evidence points towards an inflammatory component underlying pulmonary hypertension. However, the conclusive characterisation of multiple inflammatory cell populations in the lung is challenging due to the complexity of marker specificity and tissue inaccessibility. We used an unbiased computational flow cytometry approach to delineate the inflammatory landscape of idiopathic pulmonary arterial hypertension (IPAH) and healthy donor lungs.Donor and IPAH samples were discriminated clearly using principal component analysis to reduce the multidimensional data obtained from single-cell flow cytometry analysis. In IPAH lungs, the predominant CD45 cell type switched from neutrophils to CD3 T-cells, with increases in CD4 , CD8 and γδT-cell subsets. Additionally, diversely activated classical myeloid-derived dendritic cells (CD14 HLA-DR CD11c CD1a ) and nonclassical plasmacytoid dendritic cells (pDCs; CD14 CD11c CD123 HLA-DR ), together with mast cells and basophils, were more abundant in IPAH samples. We describe, for the first time, the presence and regulation of two cell types in IPAH, γδT-cells and pDCs, which link innate and adaptive immunity.With our high-throughput flow cytometry with multidimensional dataset analysis, we have revealed the interactive interplay between multiple inflammatory cells is a crucial part of their integrative network. The identification of γδT-cells and pDCs in this disease potentially provides a missing link between IPAH, autoimmunity and inflammation.