MCCIR AZ GSK Update Seminar Series
|Starts:||15:30 6 Jul 2015|
|Ends:||16:30 6 Jul 2015|
|What is it:||Seminar|
|Organiser:||Faculty of Life Sciences|
|Who is it for:||University staff, Adults, Current University students|
|Speaker:||John Grainger, Manminder Kaur|
Instruction of Inflammatory Cell Function During Acute Gastrointestinal Infection
Monocytes and neutrophils are the dominant inflammatory cell populations recruited to sites of infection and injury. Exploring the function of these cells and how their activities are conditioned in diverse tissue microenvironments is critical to improved understanding of inflammatory processes.
A major current focus of the group is to understand how and where functional diversity can be imposed on monocytes and neutrophils. In particular, we have recently found that during acute gastrointestinal infection with Toxoplasma gondii, priming of monocytes for regulatory function in the gut precedes systemic inflammation and occurs prior to their bone marrow egress. This is dependent on a previously undescribed early warning system in which mature lymphocytes in the bone marrow respond to cytokine-signals emanating from the infected gut. This work challenges the paradigm that monocyte function is dominantly imposed by local signals following tissue recruitment, and instead proposes a sequential model of differentiation in which monocytes are pre-emptively educated during development in the bone marrow to promote their tissue-specific function.
Better understanding of the mechanisms controlling monocyte regulatory function, and particularly the importance of bone marrow lymphocytes in early control of this process, may lead to the identification of novel therapeutic modalities in settings where aberrant monocyte activity has been implicated, such as in inflammatory bowel diseases (IBD) and cancer.
Airway Immune Homeostasis: Transfer of concepts to human lung disease
Kaur M, Singh D, Hussell T
Macrophages are hugely important in airway inflammation and their function is regulated by negative regulators and potentiators. In homeostasis AM are in close proximity to airway epithelial cells and their function is limited due to secretion of anti-inflammatory mediators including IL-10 & TGF? and contact mediated inhibition through negative regulators such as CD2OOR & SIRP?.During inflammation, there is a breach of epithelial integrity resulting in loss of CD200, IL-10 & TGF? allowing the macrophage to become inflammatory. Resolution of airway inflammation and tissue repair creates a new homeostatic state with altered innate responsiveness of macrophages. CD200R levels are increased above homeostasis and TLR responses are blunted, all of which limit macrophage response and significantly increases susceptibility to subsequent infections. It is unclear whether human macrophages and epithelial cells are governed by the same immune rheostat as in mice. We are investigating the importance of the inhibitory CD200:CD200R pathway in health and chronic lung inflammatory diseases in humans as well as identifying novel targets that are dysregulated in disease compared to health. We find that CD200R is upregulated in COPD macrophages compared to health. miRNA array analysis on purified airway macrophages from health & disease show miR-486-5p is 30 fold downregulated in COPD compared to health. Transmembrane emp24 domain containing protein (TMED) 7 is a target of miR-451a and preliminary data shows that this protein is upregulated in COPD airway macrophages.
Travel and Contact Information
Michael Smith Lecture Theatre
Michael Smith Building