Project description:Innate immune cells control acute eosinophilic lung inflammation induced by cystein proteases. Here we characterize the dynamic change of gene expression profile in basophils, natural helper cells and eosinophils during lung inflammation via cystein protease Examination of mRNA levels in individual cell populations, basophils, natural helper cells and eosinophils of the lung from naïve mice and papain treated mice.
Project description:Bulk RNA sequencing was performed on lung tissue from control and immune cell-specific Cyp11a1 conditional knockout (Cyp11a1fl/fl;Vav1Cre) mice following lipopolysaccharide (LPS)-induced acute lung injury. The experiment was designed to characterise genome-wide transcriptional changes associated with Cyp11a1 deficiency in immune cells during inflammation and its resolution. We collected lung samples at defined time points after LPS treatment and performed paired-end RNA sequencing. We compared transcriptomic profiles between genotypes and across time points to identify changes in inflammatory, immune-response, and tissue-repair pathways.
Project description:Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. Here we showed that ARDS patients were hypoxaemic and monocytopenic within the first 48 hours of ventilation. Monocytopenia was also observed in mouse models of acute lung injury, in which tissue hypoxia drove the suppression of type I interferon signalling in the bone marrow. This impaired monopoiesis, resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of CSF1 in mice with hypoxic lung injury rescued the monocytopenia, altered the nature of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.
