About inflammation
The Group Leads work in a highly collaborative manner with over-lapping projects, using in vitro and in vivo models for studying a variety of factors that influence leukocyte trafficking. In vitro models of the vasculature allow us to visualise the effects of blood flow on the behaviour of endothelial cells, and on the recruitment of leukocytes, platelets and stem cells.
What is inflammation?
Inflammation is the body’s natural defence against infection, injury or other harmful stimuli. When tissue is damaged, blood vessels widen and immune cells are directed to the affected site to repair damage and remove threats. This response is tightly controlled, typically short-lived and protective, allowing the body to restore balance once the trigger has passed. Too little inflammation leaves us vulnerable to infection, whereas too much or prolonged inflammation can damage healthy tissue. Understanding how inflammation is triggered, coordinated and resolved is central to preventing and treating many diseases.
Leukocyte trafficking
A central feature of inflammation is the ability of white blood cells (leukocytes) to move from the bloodstream into tissues. This process, known as leukocyte trafficking, follows a precise sequence: cells slow down, “roll” along the vessel wall, adhere firmly, then migrate between the vessel-lining cells into the tissue. In this way, immune cells are delivered where they are needed and only when they are needed.
Immune and platelet activity in the breathing lung (intravital imaging) | University of Birmingham
Stromal cells in inflammation
The tissue itself plays an active part in shaping inflammation, initially raising the alarm when it becomes damaged or infected. Cells that live within the tissue, known as stromal cells (including fibroblasts, smooth muscle cells, pericytes and tissue-resident macrophages), can communicate with vessel-lining endothelial cells to signal changes within the tissue. In response to environmental danger cues, often produced by stromal cells, endothelial cells present adhesion molecules and chemokines to guide leukocyte entry into the affected area. Once within the tissues, immune cells interact with the stromal cells to work in concert to remove the infection and repair the tissue. This close interaction between endothelial, stromal and immune cells is a major focus of our research, helping to explain why some inflammatory responses resolve while others persist.
Inflammation is a tightly regulated process that coordinates the immune cell entry and exit, along with tissue repair by stromal cells. Our team research portfolio investigates (1) how endothelial cells lining blood vessels sense of their microenvironment (both blood flow and cells within the tissue). Undertakes deep Immunophenotyping of (2) blood and (5) tissue derived cells from individuals across the life-course and how these might change in people living with immune-mediated inflammatory diseases (e.g., RA, IBD, CVD). We have Identified and are translating novel therapeutics that target (3) leukocyte trafficking and/or (7) tissue repair for patient benefit. We also examine the mechanisms regulating (4) immune cell and platelet interaction with the endothelium and/or (5) stromal cells within tissue to gain greater knowledge on what healthy responses look like and how these go wrong in disease.
Accessible image description
Accessible image description
Image shows a blood vessel lined with endothelial cells. Within the blood vessel is red blood cells and a variety of immune cells or flowing in the direction of the blood. Outside of the blood vessel are various different types of stromal cells that make up the tissue. The diagram includes a series of numbered steps depicting the types of research undertaking within the team: Endothelial sensing of their microenvironment – (1) both blood flow and cells within the tissue. Deep Immunophenotyping of (2) blood and (5) tissue derived cells from individuals across the life-course and who have immune-mediated inflammatory diseases (e.g., RA, IBD, CVD). Identification and translation of novel therapeutics that target (3) leukocyte trafficking and/or (7) tissue repair. Fundamental studies examining the mechanisms regulating (4) immune cell and platelet interaction with the endothelium and/or (5) stromal cells within tissue.
What can go wrong
Problems arise when inflammation is excessive, misdirected or long-lasting. In autoimmune disease such as rheumatoid arthritis, responses are wrongly targeted against the body’s own tissues. In allergy, harmless triggers provoke exaggerated responses. Chronic low-level inflammation is also linked to ageing and to conditions such as diabetes, inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD). In these situations, inflammation no longer protects but contributes to progressive tissue damage. In addition, disturbances at the interface between inflammation and blood clotting (thromboinflammation) can injure the microvasculature and worsen organ damage.
Accessible image description
Accessible image description
Image shows a front-facing outline of a human body with major organs illustrated. Labels identify multiple organ systems commonly affected by inflammation. The eyes are linked to dry eye and macular degeneration. The lungs are linked to chronic obstructive pulmonary disease (COPD). The heart is linked to atherosclerosis and myocardial infarction. The gastrointestinal tract is linked to inflammatory bowel disease. The skin shows psoriatic lesions. The joints and bones are linked to rheumatoid arthritis and osteoporosis. The diagram visually communicates that inflammation can have body-wide, multi-organ effects rather than being confined to a single tissue.
Why we study it
By understanding inflammation at the level of tissues, cells and molecules, we can identify where and why the immune system fails. This knowledge informs therapies that reduce harmful inflammation without compromising its essential protective functions. Our aim is to develop approaches that prevent or treat inflammation-driven disease and improve patient outcomes across a wide range of inflammatory conditions.