Role of CD1a-reactive fungal lipid-specific T cells in atopic cutaneous inflammation

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Atopic Dermatitis, more commonly known as eczema, is a common skin condition affecting up to 1 in 5 children and 1 in 12 adults. (1) The development of atopic dermatitis is believed to result from a combination of environmental and genetic factors. However, the processes underpinning its development are still not fully understood.T cells are normally involved in defence against infection, but are also known to be crucial in contributing to atopic dermatitis. Traditionally, studies of T cells have focused on their ability to recognise proteins produced by infectious microbes. However, recent evidence indicates that microbial lipids (fats) can also be recognised by a subset of these T cells. (2-4) In particular, our investigation will focus on CD1a, which can present these lipids to T cells and which has been shown to contribute to the development of atopic dermatitis. In addition, many microbial factors have been found to be linked to atopic dermatitis including fungi. However, it is not well understood how fungi contribute to disease development and severity. Therefore, I aim to improve our understanding of the role of fungi and CD1a by collecting T cells from the blood and skin of patients diagnosed with atopic dermatitis and healthy individuals. I will then investigate if any of these T cells respond specifically to fungi. In addition, I intend to study which fungal lipids are responsible for triggering this skin inflammation, and how CD1a interacts with fungal lipids and T cells structurally. In order to assess if T cells are present in the skin of atopic dermatitis patients, I will also generate skin suction blisters after injecting small amounts of fungal material into the skin of individuals; such skin challenge testing is undertaken routinely as part of allergy assessments.I would like to conduct this research to improve our understanding of how CD1a and fungi contribute to the development of atopic dermatitis. In addition, this work will generate insights into the ways in which our immune system defends us against fungi. By increasing our knowledge of how disease occurs, the work will help identify new effective treatments.References1. National Eczema Society. What is Eczema? Available from: http://www.eczema.org/what-is-eczema (Accessed 21/07/2019)2. Van Rhijn, I., Godfrey, D. I., Rossjohn, J. & Moody, D. B. Lipid and small-molecule display by CD1 and MR1. Nat. Rev. Immunol. 15, 643-654 (2015).3. Brigl, M. & Brenner, M. B. CD1: antigen presentation and T cell function. Annu. Rev. Immunol. 22, 817-890 (2004).4. Souter, M. N. et al. Identification and characterization of CD1-restricted T cells. J. Immunol. 196, 206.6--206.6 (2016).