Role of Innate Lymphoid Cells in skin inflammation
Supervisor: Prof Graham Ogg
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 and would also be able to attend the WIMM Techniques course which covers broad scientific techniques, as well as the excellent internal and guest speaker programmes available in the Weatherall Institute of Molecular Medicine.
Neill, D.R., H. Wong, A. Bellosi, R.J. Flynn, M. Daly, T.K.A. Langford, C. Bucks, C.M. Kane, P.J. Fallon, R. Pannell, H.E. Jolin, and A.N. McKenzie. 2010. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464:1367-1371.
Spits, H., D. Artis, M. Colonna, A. Diefenbach, J.P. Di Santo, G. Eberl, S. Koyasu, R.M. Locksley, A.N. McKenzie, R.E. Mebius, F. Powrie, and E. Vivier. 2013. Innate lymphoid cells - a proposal for uniform nomenclature. Nature reviews. Immunology 13:145-149.
- 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. MHCII-Mediated Dialog between Group 2 Innate Lymphoid Cells and CD4(+) T Cells Potentiates Type 2 Immunity and Promotes Parasitic Helminth Expulsion. Immunity. 2014 Aug 21;41(2):283-95. doi: 10.1016/j.immuni.2014.06.016. Epub 2014 Jul 31.
- Xue L, Salimi M, Panse I, Mjösberg JM, McKenzie AN, Spits H, Klenerman P, Ogg G. Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells. J Allergy Clin Immunol. 2014 Apr;133(4):1184-94. doi: 10.1016/j.jaci.2013.10.056. Epub 2013 Dec 31.
- Salimi M, Barlow JL, Saunders SP, Xue L, Gutowska-Owsiak D, Wang X, Huang LC, Johnson D, Scanlon ST, McKenzie AN, Fallon PG, Ogg GS. A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. J Exp Med. 2013 Dec 16;210(13):2939-50. doi: 10.1084/jem.20130351. Epub 2013 Dec 9.
For further information please contact: Prof Graham Ogg