Altered pattern of monocyte differentiation and monocyte-derived TGF-β1 in severe asthma

Chih Hsing Hung, Chin Chou Wang, Jau Ling Suen, Chau Chyun Sheu, Chang Hung Kuo, Wei Ting Liao, Yi Hsin Yang, Chao Chien Wu, Sum Yee Leung, Ruay Sheng Lai, Chi Cheng Lin, Yu Feng Wei, Chong Yeh Lee, Ming Shyan Huang, Shau Ku Huang

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Abstract

CD14+ monocytes contain precursors for macrophages and fibrocytes, known to be involved in regulating airway remodeling in human asthma and distinguishable by the PM-2K marker. We sought to identify circulating subsets of PM-2K+ macrophage-like cells and evaluate their relationships to lung function, severity and control status. Circulating PM-2K+ macrophage-like cells and fibrocytes could be identified and distinguished between normal individuals (N = 152) and asthmatic subjects (N = 133) using multi-parametric flow cytometry. PM-2K+ macrophage-like cells were found to be significantly lower in asthmatic subjects, particularly noted for the CD14-PM-2K+ subset and PM-2K+CCR7-CD86+ cells in subjects with poor lung function (FEV%/FVC% < 80%) as compared to those of normal subjects and asthmatics with normal lung function, whereas the frequency of fibrocytes was higher in asthmatics and the CCR7-CD86+ subset distribution was significantly different in subjects with varying severity. Moreover, exogenous transforming growth factor beta 1 (TGF-β1) was found to inhibit the generation of PM-2K+ macrophage-like cells, but promote the growth of fibrocytes, from CD14+ monocytes, and monocyte-derived TGF-β1 was found to correlate with the lung function, severity and control status in asthmatic patients. Collectively, aberrant differentiation of monocytes into PM-2K+ macrophage-like cell subsets and fibrocytes, together with increased monocyte-derived TGF-β1, characterized patients with severe asthma.

Original languageEnglish
Article number919
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018
Externally publishedYes

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Hung, C. H., Wang, C. C., Suen, J. L., Sheu, C. C., Kuo, C. H., Liao, W. T., Yang, Y. H., Wu, C. C., Leung, S. Y., Lai, R. S., Lin, C. C., Wei, Y. F., Lee, C. Y., Huang, M. S., & Huang, S. K. (2018). Altered pattern of monocyte differentiation and monocyte-derived TGF-β1 in severe asthma. Scientific Reports, 8(1), [919]. https://doi.org/10.1038/s41598-017-19105-z