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Title: Understanding innate lymphoid cells in allergic inflammation and respiratory viral infection
Author: Dhariwal, Jaideep
ISNI:       0000 0004 7656 9674
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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Innate Lymphoid cells (ILCs) are a novel group of effector cells of the innate immune system whose functions mirror those of known T-helper cell subsets. Animal models have shown type 2 ILCs (ILC2s) to be a critical early source of type 2 cytokines in response to both allergen and respiratory virus infection. Type 1 ILCs (ILC1s) are less well characterised but have been shown to produce IFN-γ. Analogous populations of ILC2s and ILC1s have been identified in man, however, it remains unclear what role these cells might play in orchestrating the early immune responses in asthma following both allergen and viral challenge. Moderate asthmatics and healthy controls underwent nasal allergen challenge (NAC) with grass pollen. A novel technique using flow cytometric analysis of nasal curettage samples was developed to enumerate immune cells in the nasal mucosa. Moderate asthmatics and healthy subjects were also experimentally infected with rhinovirus-16. Pulmonary ILC responses were assessed in the lower airway at baseline and at 2 time-points post infection. Asthmatics showed increased upper airway ILC2s at baseline with induction following NAC, correlating with clinical features of type 2 disease. Asthmatic patients also demonstrated increased ILC2s at baseline compared to healthy controls, further upregulated post-infection. In the lower airway, the relative balance of ILC2:ILC1s dictated exacerbation severity following rhinovirus infection. This is the first study to have identified the presence of ILC2s in the nasal mucosa of asthmatics which increases significantly after allergen challenge. Furthermore, this is the first study to analyse pulmonary ILCs from moderate-severe asthmatics during the course of an experimental rhinovirus infection and demonstrate distinct ILC profiles associated with severity of disease. The data herein applies new understanding of a population of cells of emerging importance to strengthen our knowledge of the underlying pathophysiology of asthma exacerbations.
Supervisor: Johnston, Sebastian ; Cousins, David Sponsor: Medical Research Council ; GlaxoSmithKline ; Asthma UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral