Dr Sheena Cruickshank
Worldwide, diseases of the gastrointestinal tract are amongst the most common. Despite this, relatively little is understood about gut immunology specifically how immune responses are switched on and controlled. A major theme of the lab is understanding and defining the initiation and control of immune responses in mucosal sites such as the gut and more recently the skin. In particular we focus on the mechanisms of crosstalk between immune cells and epithelial cells. My group have developed systems for the isolation and culture of primary intestinal epithelial cells and immune cells (Figure 1)
Figure 1: Micrograph of intestinal epithelial cells (red) co-cultured with T cells (green). The epithelial cells are isolated as intact crypts and maintain most of their in vivo features in culture.
By combining in vitro and in vivo approaches we have been able to characterise the barrier function of intestinal epithelial cells (IECs) and the crosstalk of IECs with immune cells, pathogens and commensal bacteria. We use infectious models such as Toxoplasma gondii, Trichuris muris and Salmonella typhimurium to answer fundamental questions about the initiation of gut immunity. Similarly, we are now addressing the role of commensal and pathogenic bacteria in the epithelial and immune response of chronic skin wounds. This work is carried out in collaboration with Dr Matthew Hardman. Our work has shown the importance of specific immune cells known as alternatively activated macrophages in wound healing and has implicated the pattern recognition receptor Nod2 as having a key role in regulating the wound healing induced inflammatory response.
Another major theme of the group is in understanding how dendritic cells (DCs) are mobilised and how they function in inflammation. DCs are critical for the development of adaptive immunity. Our group has demonstrated that epithelial mediated signals promote (DC) mobilisation. Furthermore, DC mobilisation into the gut, is strongly associated with resistance to infection. (Figure 2). We have also demonstrated a link between impaired gut DC function with the development of chronic inflammation and bone disease in colitis which is being investigated further in collaboration with colleagues in Translational medicine.
Figure 2: DCs are recruited into the colon following infection
Confocal microscope images of the colon pre (A) and 24 hours post-infection with the parasite Trichuris muris (B) showing that increased numbers of DCs (red) are found in the colon following infection. Gut epithelial cells are labelled in green and cell nuclei are labelled in blue.