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Title: The role of lymphocytes in acute lung injury
Author: Muir, Roshell
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2013
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Acute Respiratory Distress Syndrome (ARDS) is a significant problem in the critically ill. Early pathogenesis involves acute inflammation including neutrophil infiltration, the release of pro inflammatory cytokines and the influx of protein rich fluid due to the damage of the alveolar capillary barrier. Dysregulation of the inflammatory response is the main cause for lung pathology and to date there are no available pharmacological therapies. The role of myeloid cells has been described in great detail but this work represents the first detailed, systematic investigation of the role of lymphocytes during acute lung injury (ALl). Lymphocytes were shown to be present during the early development of lipopolysaccharide (LPS)-induced ALI Furthermore, elevation of lymphocyte-associated cytokines such as IL-2 was also observed; and these findings were validated in a human in vivo model and ALIl patients. Using an IL-17KO mouse model, a key role for IL-17 A in the recruitment of neutrophils to the airway was revealed. The main source of IL-17 A was attributed to the recently identified innate lymphoid cells (ILCs). It was shown that IL-17 A was produced in an IL-23-dependent manner augmented by IL-2. Detailed characterisation of the lung infiltrating ILCs suggested that they belonged to the recently classified ILC3s, previously described in the gut. Although regulatory T cells (Tregs) have been purported to play a role in the resolution phase of All, they were shown not to regulate early neutrophil recruitment, but had the capacity to downregulate cytokine-induced inflammation. Conversely, pan depletion of CD3+ T cells demonstrated a critical role for other populations of T cells in promoting pathogenesis during the acute phase of ALI; this effect is independent of IL-17 A. This work elucidates how the manipulation of lymphocyte populations may prove beneficial in developing therapeutics for the treatment of ALI patients
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available