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Shortened Telomere Length in Sputum Cells of Bronchiectasis Patients is Associated with Dysfunctional Inflammatory Pathways
Authors:Lim  Hui Fang  Tan  Nadia Suray  Dehghan  Roghayeh  Shen  Meixin  Liew  Mei Fong  Bee  Stella Wei Lee  Sia  Yee Yen  Liu  Jianjun  Khor  Chiea Chuen  Kwok  Immanuel  Ng  Lai Guan  Angeli  Veronique  Dorajoo  Rajkumar
Institution:1.Division of Respiratory and Critical Care Medicine, Department of Medicine, National University Hospital, National University Health System, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore
;2.Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
;3.Agency for Science, Technology and Research, Genome Institute of Singapore, 60 Biopolis Street, Singapore, 138672, Singapore
;4.Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
;5.Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore
;6.Department of Diagnostic Radiology, National University Hospital, National University Health System, Singapore, Singapore
;7.Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore
;8.School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
;9.State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Sciences & Peking Union Medical College, Tianjin, China
;10.Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
;11.Immunology Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine and Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, 119077, Singapore
;12.Duke-NUS Medical School Singapore, Health Services and Systems Research, Singapore, Singapore
;
Abstract:

Telomere attrition is an established ageing biomarker and shorter peripheral blood leukocyte telomere length has been associated with increased risks of respiratory diseases. However, whether telomere length in disease-relevant sputum immune cells of chronic respiratory disease patients is shortened and which pathways are dysfunctional are not clear. Here we measured telomere length from sputum samples of bronchiectasis and asthmatic subjects and determined that telomere length in sputum of bronchiectasis subjects was significantly shorter (Beta?=????1.167, PAdj?=?2.75?×?10?4). We further performed global gene expression analysis and identified genes involved in processes such as NLRP3 inflammasome activation and regulation of adaptive immune cells when bronchiectasis sputum telomere length was shortened. Our study provides insights on dysfunctions related to shortened telomere length in sputum immune cells of bronchiectasis patients.

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