Dr Lindsay Nicholson
Reader in Research
School of Cellular and Molecular Medicine,
University of Bristol, Medical Sciences Building,
Bristol, BS8 1TD
phone: +44 (0)117 33 12088 (internal 12088)
email: l.nicholson@bristol.ac.uk
group: Autoimmune Inflammation Research (AIR)
Research overview
The focus of most of the research in the laboratory is studies of the cells of the immune system. If you don’t know anything about immunology, you may want to check out our questions and answers, where we have tried to explain autoimmunity for people who haven’t studied immunology.
There are very many different cell types involved in an inflammatory reaction, but it takes at least two types of cell to make an adaptive immune response; an antigen presenting cell and an antigen specific responder cell. Our favourite examples of these are the macrophage and the CD4+ T cell. We choose these because both cell types play complimentary and crucial roles in the diseases that we study. Our research focuses on how these cells are switched on and how they might be switched off. We are particularly interested in characterising how proteins from the retina can activate specific T cells, since it is believed that CD4+ T cells co-ordinate autoimmune responses. Once they are switched on, we study how this activation process is regulated, for example by investigating the epigenetic control of cytokine genes. We also study how these cells accumulate in the eye during disease and how, once they are there, they can be activated by macrophages.
Projects relating to macrophages focus on how their interactions with molecules found in the environment modifies their function. We have studied a cytokine called tumour necrosis factor α (TNFα) extensively, because drugs that block this cytokine are an effective therapy in some forms of autoimmunity. We also study how macrophages are controlled by interactions with the extracellular matrix, especially via the matricellular protein thrombospondin-1, and by signals delivered via the cell-receptor proteins CD200 and TLR-4.
Collaborations
- Professor Andrew Dick, Ophthalmology, Bristol Eye Hospital
- Professor David Wraith, Cellular and Molecular Medicine
- Ana Anderson
- Markus Munder
- Vijay Kuchroo
Selected publications
- Nicholson, L.B., Greer, J.M., Sobel, R.A., Lees, M.A. and Kuchroo, V.K. (1995) An altered peptide ligand mediates immune deviation and prevents experimental autoimmune encephalomyelitis. Immunity 3, 397-405.
- Nicholson, L.B. and Kuchroo, V.K. (1996) Manipulation of the Th1/Th2 balance in autoimmune disease. Current opinion in immunology 8, 837-842.
- Nicholson, L.B. and Wraith, D.C. (2004) T-cell receptor degeneracy: the dog that did not bark - Adaptation of the self-reactive T-cell response to limit autoimmune disease. Molecular Immunology 40(14-15), 997-1002.
- Kerr, E.C., Copland, D.A., Dick, A.D. and Nicholson, L.B. (2008) The dynamics of leukocyte infiltration in experimental autoimmune uveoretinitis. Progr. Retin. Eye Res. 27, 527-535.
- Nicholson, L.B., Raveney, B.J.E. and Munder, M. (2009) Monocyte Dependent Regulation of Autoimmune Inflammation. Curr. Mol. Med. 9, 23-29.
Recent Publications
- Khera, T.K., Dick, A.D. and Nicholson, L.B. (2010) Mechanisms of TNF? regulation in uveitis: Focus on RNA-binding proteins. Progress in Retinal and Eye Research 29, 610-621.
- Khera, T.K., Dick, A.D. and Nicholson, L.B. (2010) Fragile X-related protein FXR1 controls post-transcriptional suppression of lipopolysaccharide-induced tumour necrosis factor-alpha production by transforming growth factor-beta1. FEBS J, 277, 2754-2765.
- Wu, W., Llewellyn, O.P., Bates, D.O., Nicholson, L.B. and Dick, A.D. (2010) IL-10 regulation of macrophage VEGF production is dependent on macrophage polarisation and hypoxia. Immunobiology, 215, 796-803.
- Copland, D.A., Hussain, K., Baalasubramanian, S., Hughes, T.R., Morgan, B.P., Xu, H., Dick, A.D. and Nicholson, L.B. (2010) Systemic and local anti-C5 therapy reduces the disease severity in experimental autoimmune uveoretinitis. Clin. Exp. Immunol, 159, 303-314.
- Raveney, B.J.E., Copland, D.A., Calder, C.J., Dick, A.D. and Nicholson, L.B. (2010) TNFR1 signalling is a critical checkpoint for developing macrophages that control T-cell proliferation. Immunology, 131, 340-349.