The aim of the group is to understand, at the molecular and cellular level, the role of human cutaneous immune responses in mechanisms of disease, treatment and vaccination. As well as contributing to an understanding of disease pathogenesis, we aim to translate our findings to changes in clinical practice.
Skin frequently represents the first point of contact with pathogens and allergens, yet we still know relatively little of the role of the skin barrier and skin immune system in reacting to such challenges. This is crucially important in understanding the mechanisms of skin diseases and related diseases, and for optimising approaches to cutaneous drug and vaccine delivery.
We have an ongoing interest in skin T cell responses, specifically how these can be initiated and propagated. In the past, we have designed and implemented MHC tetramer technology and defined peptide antigen-specific T cell populations in patients with allergies to house dust mite (HDM) and cat dander; we have also been investigating immune responses to varicella zoster virus (VZV). We are currently focusing on lipid-specific CD1a-restricted T cell responses, including the involvement of phospholipase A2 (PLA2). We determined that the PLA2 enzyme can generate new lipid antigens (“neo-antigens”) in the skin and induce immune responses contributing to allergy, with important roles in atopic dermatitis (AD) and other skin diseases such as psoriasis.
We are also investigating populations of innate lymphoid cells (ILCs), which have recently been identified as a new cell type in the skin and other sites. For the past few years we have been defining the role and requirements of these cells and their cross-talk with keratinocytes within the epidermis.
Moreover, we also investigate the effect of ongoing immune responses on the epithelial component of the skin barrier. We determined that inflammatory mediators, such as cytokines and histamine, affect the integrity and function of the skin. Finally, we are interested in epidermal biology and recently helped define mechanisms governing epidermal differentiation and stratification.
We also use our findings to understand conditions which affect other organ systems; an example is dengue virus which infects 390 million people worldwide annually. We have found that some of the immunological processes we are finding in the skin, can be shared with immune responses to dengue virus.
The studies conducted within the group attempt to resolve fundamental questions related to immunology and translate these towards novel therapeutic strategies.
Professor Vincenzo Cerundolo, MRC Human Immunology Unit, University of Oxford
Professor Gathsaurie Malavige, University of Sri Jayawardenapura, Sri Lanka
We take an active role in Public Engagement through Exhibits, School talks, public talks, blogs and podcasts.
Clinical studies and trials
We continually translate our findings through to patients, and undertake early and late phase clinical trials with an experimental medicine focus.