Role of IL-33 on human mast cell responses to rhinovirus infection in asthma.
Lead Research Organisation:
University of Southampton
Department Name: Inflammation Infection Immunology
Abstract
Skills Priority Alignment: Interdisciplinary and Quantitative Biology.
Asthma is an inflammatory disease of the airways in which various factors are involved. Many studies have shown that human rhinovirus (RV) plays a major role in both asthma aetiology and pathogenesis. Infection with RV in early life was found to be a predictor for asthma development in later life. In addition, RV is also the leading cause for viral-induced exacerbations in children with asthma. The primary site for RV replication and release are bronchial epithelial cells (BECs). In asthma, there is an increased number of mast cells (MCs) found at the bronchial epithelium, which situates MCs to be in direct contact with both BECs and RV. MCs implicated in asthma have a disease phenotype where they have increased expression of FCERI which binds IgE at high-affinity. The increased infiltration of these phenotypically different MCs at the bronchial epithelium results in cross-talk with BECs which contributes to the asthma phenotype. For example, BECs release stem cell factor which is crucial for MC survival and MCs respond to epithelial-derived cytokines including IL-33, which enhances MC responses. However, BECs are also capable of suppressing IgE-dependent histamine secretion from MCs. Upon interaction with MCs, BECs will release IL-6, CXCL1 and CXCL8, which contributes to local inflammatory responses, and PAI-1 which contributes to airway remodelling. MCs are further implicated in asthma as it has been recently shown in the lab that they support RV replication and release, indicating that MCs may act as another reservoir for RV release during exacerbations. This project aims to use a transcriptomic approach to identify the global gene response of MCs in asthma during RV infection and in the presence of IL-33, to understand MC cell function and cell changes during infection.
Aim: Obtain the global gene response of mast cells in response to IL-33 and rhinovirus.
Objective 1: Obtain the transcriptomic profile of the MC cell line, LAD2, after HRV infection and IL-33 treatment.
Objective 2: To validate expression of genes of interest from differentially expressed genes at the protein level.
Objective 3: To validate gene and protein expression levels in cord-blood derived mast cells (CBMCs)
Asthma is an inflammatory disease of the airways in which various factors are involved. Many studies have shown that human rhinovirus (RV) plays a major role in both asthma aetiology and pathogenesis. Infection with RV in early life was found to be a predictor for asthma development in later life. In addition, RV is also the leading cause for viral-induced exacerbations in children with asthma. The primary site for RV replication and release are bronchial epithelial cells (BECs). In asthma, there is an increased number of mast cells (MCs) found at the bronchial epithelium, which situates MCs to be in direct contact with both BECs and RV. MCs implicated in asthma have a disease phenotype where they have increased expression of FCERI which binds IgE at high-affinity. The increased infiltration of these phenotypically different MCs at the bronchial epithelium results in cross-talk with BECs which contributes to the asthma phenotype. For example, BECs release stem cell factor which is crucial for MC survival and MCs respond to epithelial-derived cytokines including IL-33, which enhances MC responses. However, BECs are also capable of suppressing IgE-dependent histamine secretion from MCs. Upon interaction with MCs, BECs will release IL-6, CXCL1 and CXCL8, which contributes to local inflammatory responses, and PAI-1 which contributes to airway remodelling. MCs are further implicated in asthma as it has been recently shown in the lab that they support RV replication and release, indicating that MCs may act as another reservoir for RV release during exacerbations. This project aims to use a transcriptomic approach to identify the global gene response of MCs in asthma during RV infection and in the presence of IL-33, to understand MC cell function and cell changes during infection.
Aim: Obtain the global gene response of mast cells in response to IL-33 and rhinovirus.
Objective 1: Obtain the transcriptomic profile of the MC cell line, LAD2, after HRV infection and IL-33 treatment.
Objective 2: To validate expression of genes of interest from differentially expressed genes at the protein level.
Objective 3: To validate gene and protein expression levels in cord-blood derived mast cells (CBMCs)
Organisations
People |
ORCID iD |
| Emily Swindle (Primary Supervisor) | |
| Chiara Banas (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N014308/1 | 01/10/2016 | 30/09/2025 | |||
| 1820247 | Studentship | MR/N014308/1 | 01/10/2016 | 31/08/2021 | Chiara Banas |
| Description | Medicine Student Mobility Fund - Presidential Scholarship |
| Amount | £1,700 (GBP) |
| Organisation | University of Southampton |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 06/2019 |
| End | 07/2019 |