Arthritis Research UK
Professor of Inflammation Biology
+44(0)20 7848 8630
The general theme of the lab is the understanding of cell signalling pathways and transcriptional mechanisms that regulate the functional polarisation of macrophages and dendritic cells (DC) in inflammation and immunity. Macrophage and DC activation by microbial pattern recognition receptors, such as Toll like receptors (TLRs), is critical for innate and adaptive immunity and has been extensively studied. However, these cells also play important roles in the resolution of inflammation, maintaining tissue homeostasis and immune-tolerance, but we understand relatively little about the signalling pathways and molecular mechanisms that mediate the functions of macrophages and DC in this context. In infectious diseases and cancer, these mechanisms promote evasion of protective immunity and disease progression. On the other hand, deregulation of these mechanisms may also lead to chronic inflammatory disease and autoimmunity.
Our previous work showed the prototypical pro-inflammatory transcription factor, Nuclear Factor-kB (NF-kB), actually has an important role in the resolution of inflammation by limiting macrophage activation during infection. In parallel studies, we showed that NF-kB activation in tumour-associated macrophages (TAM) maintained an anti-inflammatory phenotype associated with tumour progression and suppression of anti-tumour immunity. More recently, we discovered that IKKb-mediated activation of the canonical NF-kB pathway plays a critical role in the maturation of tolerogenic DC and regulatory T cell (Treg) conversion – required to maintain peripheral tolerance and immune homeostasis. Our ongoing studies are focused on further characterisation of the signalling pathways in macrophages and DC that dictate the balance between pro- and anti-inflammatory functions or immune-stimulatory versus immune-suppressive activity.
Our lab has a dual affiliation with the Centre d’Immunologie Marseille Luminy (CIML). The CIML is an internationally renowned Immunology research institute created by the CNRS, INSERM and Aix-Marseille-Université. It is located on a pluridisciplinary campus east of the city of Marseille in the south of France