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Systemic and Intercellular Gene Networks Underlying RV-Induced Airways Disease

Sponsored by National Institute of Allergy and Infectious Disease

$268.6K Funding
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Respiratory viral infections trigger wheezing illnesses in children and increase the risk that these children willgo on to develop asthma. It is now recognized that asthma is not created equal among children. There aredifferent forms of asthma and risk for asthma is highest among wheezing children who also have allergies. It iscurrently not well understood why children with wheezing and allergies are more susceptible to respiratory viralinfections and more likely to develop asthma. However an important clue from our previous studies is that theimmune factors that are associated with risk versus protection to virus-induced wheezing can be found locallyin the airways and lung and also systematically in the blood and bone marrow. This suggested our overarchinghypothesis that the immunological mechanisms that determine susceptibility to virus-induced wheezing operateboth locally and systemically through a lung-blood-bone marrow axis. Here we will study systemic immuneresponses to viruses in children with or without wheezing allergic inflammation or both. The research willentail culturing blood-derived immune cells from the children in the presence or absence of a virus. Molecularprofiling technologies will be employed to characterize immune responses to the virus at the resolution ofsingle cells and the responses will be compared and contrasted in groups of children with or without wheezingand/or allergic inflammation. We hypothesize that risk for asthma is determined by the balance of the biologicalactivity of two immune factors that control immune responses to viruses: Interferon regulatory factor 7 (IRF7)and the high-affinity immunoglobulin E receptor subunit gamma (FCER1G). We additionally hypothesize that ahighly specialized population of immune cells called dendritic cells control the balance of IRF7 and FCER1Gactivity. The findings from this study are important because asthma affects 1 in 13 Americans and is the mostcommon chronic disease among children. Each year in the United States asthma accounts for more than 5million GP visits more than 1.5 million visits to the emergency department and almost 200000 dischargesfrom hospital inpatient care. Moreover approximately 11 people die from asthma every day in the UnitedStates. Understanding the immunological and molecular factors that determine asthma risk will pave the wayfor the development of new approaches to treat or prevent asthma and reduce the overall burden of thisdisease on children and their families.