Hui Li1, Huaqi Wang1, Leon Sokulsky2, Shaoxia Liu1, Rui Yang1, Xiaojie Liu3, Lujia Zhou3, Juan Li1, Chun Huang1, Fangfang Li1, Xu Lei1, Hongxia Jia1, Jiuling Cheng1, Fuguang Li3, Ming Yang4, Guojun Zhang5. 1. Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 2. Priority Research Centre for Healthy Lungs, School of Biomedical Sciences and Pharmacy, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Callaghan, Australia. 3. Academy of Medical Sciences and Department of Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China. 4. Priority Research Centre for Healthy Lungs, School of Biomedical Sciences and Pharmacy, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Callaghan, Australia; Academy of Medical Sciences and Department of Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China. Electronic address: ming.yang@newcastle.edu.au. 5. Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: gjzhangzzu@126.com.
Abstract
BACKGROUND: Asthma exacerbations are associated with heightened asthma symptoms, which can result in hospitalization in severe cases. However, the molecular immunologic processes that determine the course of an exacerbation remain poorly understood, impeding the progression of development of effective therapies. OBJECTIVE: Our aim was to identify candidate genes that are strongly associated with asthma exacerbation at a cellular level. METHODS: Subjects with asthma exacerbation and healthy control subjects were recruited, and bronchoalveolar lavage fluid was isolated from these subjects via bronchoscopy. Cells were isolated through fluorescence-activated cell sorting, and single-cell RNA sequencing was performed on enriched cell populations. RESULTS: We showed that the levels of monocytes, CD8+ T cells, and macrophages are significantly elevated in the bronchoalveolar lavage fluid of patients. A set of cytokines and intracellular transduction regulators are associated with asthma exacerbations and are shared across multiple cell clusters, forming a complicated molecular framework. An additional group of core exacerbation-associated modules is activated, including eukaryotic initiation factor 2 signaling, ephrin receptor signaling, and C-X-C chemokine receptor type 4 signaling in the subpopulations of CD8+ T cells (C1-a) and monocyte clusters (C7 clusters), which are associated with infection. CONCLUSION: Our study identified a significant number of severe asthma-associated genes that are differentially expressed by multiple cell clusters.
BACKGROUND:Asthma exacerbations are associated with heightened asthma symptoms, which can result in hospitalization in severe cases. However, the molecular immunologic processes that determine the course of an exacerbation remain poorly understood, impeding the progression of development of effective therapies. OBJECTIVE: Our aim was to identify candidate genes that are strongly associated with asthma exacerbation at a cellular level. METHODS: Subjects with asthma exacerbation and healthy control subjects were recruited, and bronchoalveolar lavage fluid was isolated from these subjects via bronchoscopy. Cells were isolated through fluorescence-activated cell sorting, and single-cell RNA sequencing was performed on enriched cell populations. RESULTS: We showed that the levels of monocytes, CD8+ T cells, and macrophages are significantly elevated in the bronchoalveolar lavage fluid of patients. A set of cytokines and intracellular transduction regulators are associated with asthma exacerbations and are shared across multiple cell clusters, forming a complicated molecular framework. An additional group of core exacerbation-associated modules is activated, including eukaryotic initiation factor 2 signaling, ephrin receptor signaling, and C-X-C chemokine receptor type 4 signaling in the subpopulations of CD8+ T cells (C1-a) and monocyte clusters (C7 clusters), which are associated with infection. CONCLUSION: Our study identified a significant number of severe asthma-associated genes that are differentially expressed by multiple cell clusters.
Authors: Xiaojie Liu; Keilah G Netto; Leon A Sokulsky; Lujia Zhou; Huisha Xu; Chi Liu; Ming Wang; Huaqi Wang; Hui Li; Guojun Zhang; Paul S Foster; Fuguang Li; Ming Yang Journal: Mucosal Immunol Date: 2022-08-29 Impact factor: 8.701
Authors: Alisha M Smith; Nathan Harper; Justin A Meunier; Anne P Branum; Fabio Jimenez; Lavanya Pandranki; Andrew Carrillo; Charles S Dela Cruz; Marcos I Restrepo; Diego J Maselli; Cynthia G Rather; Anna H Heisser; Daniel A Ramirez; Weijing He; Robert A Clark; Charles P Andrews; Scott E Evans; Jacqueline A Pugh; Nu Zhang; Grace C Lee; Alvaro G Moreira; Leopoldo N Segal; Robert M Ramirez; Robert L Jacobs; Muthu Saravanan Manoharan; Jason F Okulicz; Sunil K Ahuja Journal: J Allergy Clin Immunol Date: 2021-01-23 Impact factor: 14.290
Authors: Alisha M Smith; Robert M Ramirez; Nathan Harper; Fabio Jimenez; Anne P Branum; Justin A Meunier; Lavanya Pandranki; Andrew Carrillo; Caitlyn Winter; Lauryn Winter; Cynthia G Rather; Daniel A Ramirez; Charles P Andrews; Marcos I Restrepo; Diego J Maselli; Jacqueline A Pugh; Robert A Clark; Grace C Lee; Alvaro G Moreira; Muthu Saravanan Manoharan; Jason F Okulicz; Robert L Jacobs; Sunil K Ahuja Journal: Allergy Date: 2021-10-22 Impact factor: 14.710
Authors: Ji Young Kim; Patrick Stevens; Manjula Karpurapu; Hyunwook Lee; Joshua A Englert; Pearlly Yan; Tae Jin Lee; Navjot Pabla; Maciej Pietrzak; Gye Young Park; John W Christman; Sangwoon Chung Journal: Front Immunol Date: 2022-07-26 Impact factor: 8.786