Role of Innate Lymphoid Cells in skin inflammation
Innate lymphoid cells are a novel family of cells that are believed to play a role in many inflammatory diseases. Type 2 innate lymphoid cells (ILC2, nuocytes) express type 2 cytokines and may play a role in defence against parasites and wound healing, but may also contribute to allergic disease. We have recently observed ILC2 are present in the skin of humans and infiltrate further within lesions of atopic eczema. We have defined a number of cell surface molecules which are expressed by ILC2 and are likely to play a role in their function. These include activatory and inhibitory receptors and molecules likely to be required for migration towards inflammatory skin environments.
The aim of the project is to define the role of the activatory and inhibitory receptors in ILC2 function, with the long term aim of influencing ILC2 function through novel therapeutics. We have recruited a large cohort of individuals with atopic eczema and other inflammatory skin diseases, as well as healthy controls. We can isolate and grow ILC2 from blood and human skin and so all the relevant sample sources and techniques are in place. Once isolated, the work will involve the further definition of molecules associated with ILC2 and undertaking functional investigations. The approaches will include flow cytometry, expression analyses (eg high throughput sequencing), multiplex cytokine analyses, ELISpot, cell transfection, migration assays, immunohistochemistry.
This translational project is based at the Weatherall Institute of Molecular Medicine, within the MRC Human Immunology Unit. There are excellent core facilities, infrastructure and expertise readily available. The student would receive training in molecular and cellular immunology techniques as above. In addition the student would gain experience in handling human skin biopsies and growing keratinocytes, with concomitant assays including imaging, microarray, rtPCR and Western Blot. The student would also learn about regulatory issues surrounding the use and storage of human samples including ethics, hospital R&D, GCP and HTA. The student would attend GCP, statistical courses and relevant conferences.
As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford. Students are also able to attend the Methods and Techniques course run by the MRC Weatherall Institute of Molecular Medicine. This course runs through the year, ensuring that students have the opportunity to build a broad-based understanding of differing research techniques.
Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.
The department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to support the careers of female students and staff.
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|3||Oliphant CJ, Hwang YY, Walker JA, Salimi M, Wong SH, Brewer JM, Englezakis A, Barlow JL, Hams E, Scanlon ST, Ogg GS, Fallon PG, McKenzie AN. 2014. MHCII-mediated dialog between group 2 innate lymphoid cells and CD4(+) T cells potentiates type 2 immunity and promotes parasitic helminth expulsion.Immunity, 41 (2), pp. 283-95. - http://www.ncbi.nlm.nih.gov/pubmed/25088770|
|4||Saunders SP, Moran T, Floudas A, Wurlod F, Kaszlikowska A, Salimi M, Quinn EM, Oliphant CJ, Núñez G, McManus R, Hams E, Irvine AD, McKenzie AN, Ogg GS, Fallon PG. 2016. Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary lung inflammation of the atopic march requiring adaptive immunity.J. Allergy Clin. Immunol., 137 (2), pp. 482-91. - http://www.ncbi.nlm.nih.gov/pubmed/26299987|
|5||Salimi M, Xue L, Jolin H, Hardman C, Cousins DJ, McKenzie AN, Ogg GS. 2016. Group 2 Innate Lymphoid Cells Express Functional NKp30 Receptor Inducing Type 2 Cytokine Production.J. Immunol., 196 (1), pp. 45-54. - http://www.ncbi.nlm.nih.gov/pubmed/26582946|
Salimi M, Stöger L, Liu W, Go S, Pavord I, Klenerman P, Ogg G, Xue L. Cysteinyl leukotriene E(4) activates human group 2 innate lymphoid cells and enhances the effect of prostaglandin D(2) and epithelial cytokines. J Allergy Clin Immunol. 2017 Jan 20. pii: S0091-6749(17)30051-9. doi: 10.1016/j.jaci.2016.12.958. PubMed PMID: 28115217