University of BristolAutoimmune Inflammation Research

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T cell in blood

Investigators and Projects

Lindsay Nicholson

Andrew Dick

Overview of research

T cell macrophage interactions

Properties of eye autoantigens

Inflammation and angiogenesis

Leucocyte populations in EAU

Steroid resistance

CD200 in EAU

Complement and ocular disease

Modelling Immune responses in silico

Selected References

Vision Research 2007

Vision Research 2008

Vision Research 2009

Recent Advances

Our Research

Selected References


GJ Jaffe, AD Dick, et al. (2016). Adalimumab in Patients with Active Noninfectious Uveitis. New England Journal of Medicine 375 : 932-943 DOI: 10.1056/NEJMoa1509852

JH Wu, W Su, MB Powner, J Liu, DA Copland, M Fruttiger, P Madeddu, AD Dick, L Liu (2016). Pleiotropic action of CpG-ODN on endothelium and macrophages attenuates angiogenesis through distinct pathways. Scientific Reports 6 Article 31873 DOI: 10.1038/srep31873

CJ Chu, PJ Gardner, DA Copland, SE Liyanage, A Gonzalez-Cordero, SMK Holthaus, UFO Luhmann, AJ Smith, RR Ali, AD Dick (2016) Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse modelDisease models and mechanisms 9: 473-481 DOI: 10.1242/dmm.022475

J Liu, DA Copland, S Theodoropoulou, HAA Chiu, MD Barba, KW Mak, M Mack, LB Nicholson, AD Dick (2016). Impairing autophagy in retinal pigment epithelium leads to inflammasome activation and enhanced macrophage-mediated angiogenesis. Scientific Reports 6 Article 20639 DOI: 10.1038/srep20639

LB Nicholson (2016). The Immune System. Essays in Biochemistry 60: 275-301 DOI: 10.1042/EBC20160017


S Yazid, PJ Gardner, L Carvalhoa, CJ Chua, RJ Flower, E Solito, RWJ Lee, RR Ali, AD Dick (2015). Annexin-A1 restricts Th17 cells and attenuates the severity of autoimmune disease. J Autoimmunity 58:1-11 doi: 10.1016/j.jaut.2014.12.004

LP Schewitz-Bowers, PJP Lait, DA Copland, P Chen, W Wu, AD Dhanda, B Vistica, EL Williams, B Liu, S Jawad ,Z Li, W Tucker, S Hirani, Y Wakabayashi, J Zhug, H. Nida Sen, B Conway-Campbell, I Gery, AD Dick, Lai Wei, RB Nussenblatt, RWJ Lee (2015). Glucocorticoid Resistant Th17 Cells are Selectively Attenuated by Cyclosporine A Proc Nat Acad Sci (USA) 112:4080-5

G Crawford, J Boldison, DA Copland, P Adamson, D Gale, M Brandt, LB Nicholson, AD Dick (2015). The Role of Lipoprotein-Associated Phospholipase A2 in a murine model of Experimental Autoimmune Uveoretinitis. PLos One 10: e0122093. doi: 10.1371

W-K Wu, A Georgiadis, DA Copland, S Liyanage, UF Luhmann, SJ Robbie, J Liu, J Wu, JW Bainbridge, DO Bates, RR Ali, LB Nicholson, AD Dick (2015). IL-4 regulates specific Arg-1+ macrophage sFlt-1-mediated inhibition of angiogenesis. Am J Path 185: 2324–2335 doi: 10.1016/j.ajpath.2015.04.013.

Boldison, J., T.K. Khera, D.A. Copland, M.L. Stimpson, G.L. Crawford, A.D. Dick, and L.B. Nicholson. (2015). A novel pathogenic RBP-3 peptide reveals epitope spreading in persistent Experimental Autoimmune Uveoretinitis. Immunol 146:301-311.


Lee, R.W.J., L.B. Nicholson, H.N. Sen, C.C. Chan, L. Wei, R.B. Nussenblatt, and A.D. Dick. (2014) Autoimmune and autoinflammatory mechanisms in uveitis.
Seminars in Immunopathology doi: 10.1007/s00281-014-0433-9

Boldison, J., C.J. Chu, D.A. Copland, P.J.P. Lait, T.K. Khera, A.D. Dick, and L.B. Nicholson. (2014) Tissue-Resident Exhausted Effector Memory CD8+ T Cells Accumulate in the Retina during Chronic Experimental Autoimmune Uveoretinitis. J. Immunol 192: 4541-4550

Little, J.A., E.S. Sen, H. Strike, A. Hinchcliffe, C.M. Guly, R.W.J. Lee, A.D. Dick, and A.V. Ramanan. (2014) The Safety and Efficacy of Noncorticosteroid Triple Immunosuppressive Therapy in the Treatment of Refractory Chronic Noninfectious Uveitis in Childhood. Journal of Rheumatology 41: 136-139.


Horie, S., S.J. Robbie, J. Liu, W.-K. Wu, R.R. Ali, J.W. Bainbridge, L.B. Nicholson, M. Mochizuki, A.D. Dick, and D.A. Copland. (2013) CD200R signaling inhibits pro-angiogenic gene expression by macrophages and suppresses choroidal neovascularization. Scientific Reports 3: 3072 doi:10.1038/srep03072

Liu, J., Copland, D. A., Horie, S., Wu, W-K., Chen, M., Xu, Y., Paul Morgan, B., Mack, M., Xu, H., Nicholson, L. B. & Dick, A. D. (2013) Myeloid cells expressing VEGF and arginase-1 following uptake of damaged retinal pigment epithelium suggests potential mechanism that drives the onset of choroidal angiogenesis in mice PloS one 8: e72935 doi: 10.1371/journal.pone.0072935

Chu C.J., Herrmann P., Carvalho L.S., Liyanage S..E, Bainbridge J.W.B., Ali, R.R, Dick A.D., Luhmann U.F.O. (2013) Assessment and In Vivo Scoring of Murine Experimental Autoimmune Uveoretinitis Using Optical Coherence Tomography. PloS one 8: e63002. doi:10.1371/journal.pone.0063002

Gammons, M.V., O. Fedorov, D. Ivison, C. Du, T. Clark, C. Hopkins, M. Hagiwara, A.D. Dick, R. Cox, S.J. Harper, J.C. Hancox, S. Knapp, and D.O. Bates. (2013) Topical Antiangiogenic SRPK1 Inhibitors Reduce Choroidal Neovascularization in Rodent Models of Exudative AMD. Invest Ophthalmol Vis Sci 54: 6052-6062.

Gammons, M.V.R., A.D. Dick, S.J. Harper, and D.O. Bates. (2013) SRPK1 Inhibition Modulates VEGF Splicing to Reduce Pathological Neovascularization in a Rat Model of Retinopathy of Prematurity. Invest Ophthalmol Vis Sci 54: 5797-5806.


Fordham, J.B., Hua, J., Moorwood, S.R., Schewitz-Bowers, L.P., Copland, D.A., Dick, A.D. & Nicholson, L.B. (2012) Environmental conditioning in the control of macrophage thrombospondin-1 production
Scientific Reports 2: 512 doi:10.1038/srep00512

Blyuss, K.B. & Nicholson, L.B. (2012) The role of tunable activation thresholds in the dynamics of autoimmunity
Journal of Theoretical Biology 308: 45-55.

Nicholson, D., Kerr, E., Jepps, O. & Nicholson, L.B. (2012) Modelling experimental uveitis: barrier effects in autoimmune disease
Inflammation Research doi:10.1007/s00011-012-0469-z.

Wraith, D. C. & Nicholson, L. B. (2012) The adaptive immune system in diseases of the central nervous system.
The Journal of Clinical Investigation 122: 1172-1179.

Lee, R. W. J., Dick, A. D. (2012) Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation
Eye 26: 17-28.

Khera, T. K., Copland, D. A., Boldison, J., Lait, P. J. P., Szymkowski, D. E., Dick, A. D. & Nicholson, L. B. (2012)TNF-mediated macrophage activation in the target organ is critical for clinical manifestation of uveitis. Clinical & Experimental Immunology 168: 165-177.

Copland, D.A., Liu, J., Schewitz-Bowers, L.P., Brinkmann, V., Anderson, K., Nicholson, L.B., Dick, A.D. (2012) Therapeutic Dosing of Fingolimod (FTY720) Prevents Cell Infiltration, Rapidly Suppresses Ocular Inflammation, and Maintains the Blood-Ocular Barrier
American Journal of Pathology 180: 672-681.

Chen, M., Copland, D.A., Zhao, J., Liu, J., Forrester, J.V., Dick, .D., Xu, H. (2012) Persistent Inflammation Subverts Thrombospondin-1-Induced Regulation of Retinal Angiogenesis and Is Driven by CCR2 Ligation
American Journal of Pathology 180: 235-245.


Koukounis, D., Nicholson, L., Bull, D. R. & Achim, A. (2011) Retinal image registration based on multiscale products and optic disc detection
IEEE Engineering in Medicine and Biology Society Conference 2011: 6242-6245.

Sood, A., Salih, S., Roh, D., Lacharme-Lora, L., Parry, M., Hardiman, B., Keehan, R., Grummer, R., Winterhager, E., Gokhale, P. J., Andrews, P. W., Abbott, C., Forbes, K., Westwood, M., Aplin, J. D., Ingham, E., Papageorgiou, I., Berry, M., Liu, J., Dick, A. D., Garland, R. J., Williams, N., Singh, R., Simon, A. K., Lewis, M., Ham, J., Roger, L., Baird, D. M., Crompton, L. A., Caldwell, M. A., Swalwell, H., Birch-Machin, M., Lopez-Castejon, G., Randall, A., Lin, H., Suleiman, M-S., Evans, W. H., Newson, R., Case, C. P. (2011) Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticles depends on barrier thickness
Nature Nanotechnology 6: 824-833.

Sell, E. S., Mandal, K., Dick, A. D., Ramanan, A., V (2011) Use of adalimumab in juvenile idiopathic arthritis-associated refractory uveitis: efficacy in ocular disease - a retrospective case series
Clinical and Experimental Rheumatology 29: 442.

Sharma, S.M., Martin, T.M., Rose, C.D., Dick, A.D., Ramanan, A.V. (2011) Distinguishing between the innate immune response due to ocular inflammation and infection in a child with juvenile systemic granulomatous disease treated with anti-TNF-alpha monoclonal antibodies
Rheumatology 50: 990-992.

Atan, D., Fraser-Bell, S., Plskova, J., Kuffova, ., Hogan, A., Tufail, A., Kilmartin, D.J., Forrester, J.V., Bidwell, J.L., Dick, A.D., Churchill, A.J. (2011) Punctate Inner Choroidopathy and Multifocal Choroiditis with Panuveitis Share Haplotypic Associations with IL10 and TNF Loci
Investigative Ophthalmology & Visual Science 52: 3573-3581.


Khera, T. K.,Dick A. D. and Nicholson L. B. (2010) Mechanisms of TNF alpha regulation in uveitis: Focus on RNA-binding proteins
Progress in Retinal and Eye Research 29: 610-621.

Wu W.K., 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.

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.
DOI: 10.1111/j.1365-2567.2010.03305.x

Schewitz-Bowers, L. P., Lee, R. W. J. and Dick A.D. (2010) Immune mechanisms of intraocular inflammation
Expert Review of Ophthalmology 5: 43-58

T. K. Khera, A. D. Dick and L. B. Nicholson (2010) Fragile-X-related protein FXR1 controls post-transcriptional suppression of lipopolysaccharide-induced tumour necrosis factor-alpha; production by transforming growth factor-beta1
FEBS Journal 277: 2754-2765

D. A. Copland, K. Hussain, S. Baalasubramanian, T. R. Hughes, B. P. Morgan, H. Xu, A. D. Dick and L. B. Nicholson (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., Dick, A. D., and Nicholson, L. B. (2009) TNFR1-Dependent Regulation of Myeloid Cell Function in Experimental Autoimmune Uveoretinitis, J. Immunol 183: 2321-2329

Lee, R. W. J., Schewitz, L. P., Nicholson, L. B., Dayan, C. M., and Dick, A. D. (2009) Steroid Refractory CD4+ T Cells in Patients with Sight-Threatening Uveitis, Invest.Ophthalmol.Vis.Sci. 50: 4273-4278

Schewitz, L.P. Lee, R.W. Dayan, C.M. and Dick, A. D. (2009) Glucocorticoids and the emerging importance of T cell subsets in steroid refractory diseases Immunopharmacology & Immunotoxicology 31: 1-22

Carter, D.A. Dick, A.D. and Mayer, E.J. CD133+ adult human retinal cells remain undifferentiated in Leukaemia Inhibitory Factor (LIF) BMC Ophthalmology 9 1

Nicholson, L. B., Raveney, B. J. E., and Munder, M. (2009) Monocyte dependent regulation of autoimmune inflammation.
Current Molecular Medicine 9: 23-29


Kerr, E. C., Raveney, B. J. E., Copland, D. A., Dick, A. D., and Nicholson, L. B. (2008). Analysis of Retinal Cellular Infiltrate in Experimental Autoimmune Uveoretinitis Reveals Multiple Regulatory Cell Populations.
J. Autoimmunity 31: 354-361

Kerr, E. C., Copland, D. A., Dick, A. D., and Nicholson, L. B. (2008). The dynamics of leukocyte infiltration in experimental autoimmune uveoretinitis.
Progress in Retinal and Eye Research 27: 527-535

Raveney, B. J. E., Copland, D. A., Nicholson, L. B., and Dick, A. D. (2008) Fingolimod (FTY720) as an acute rescue therapy for intraocular inflammatory disease.
Archives of Ophthalmology. 126: 1390-1395

Copland, D. A., Wertheim, M. S., Raveney, B. J. E., Armitage, W J.., Nicholson, L. B., and Dick, A. D. (2008). The clinical time-course of experimental autoimmune uveoretinitis using topical endoscopic fundal imaging with histological and cellular infiltrate correlation
Invest. Ophthalmol. Vis. Sci. 49: 5458-5465 doi:10.1167/iovs.08-2348

Raveney, B.J.E., Richards C.M., Aknin,M-L., Copland,D.A., Burton,B.R., Kerr,E.C., Nicholson,L.B., Williams,N.A., and Dick,A.D. (2008) The B subunit of Escherichia coli heat-labile enterotoxin inhibits Th1 but not Th17 cell responses in established autoimmune uveoretinitis
Invest. Ophthalmol. Vis. Sci. 49: 4008-4017 doi:10.1167/iovs.08-1848

Nicholson, D. and Nicholson, L.B. (2008) A simple immune system simulation reveals optimal movement and cell density parameters for successful target clearance. Immunology 123: 519-527 doi:10.1111/j.1365-2567.2007.02721.x


Lee,R.W.J., T.J.Creed, L.P.Schewitz, P.V.Newcomb, L.B.Nicholson, A.D.Dick, and C.M.Dayan. (2007). CD4+CD25int T Cells in Inflammatory Diseases Refractory to Treatment with Glucocorticoids. J. Immunol. 179: 7941-7948.

Imrie, F.R. and Dick, A.D. (2007). Biologics in the treatment of uveitis.
Curr Opin Ophthalmol 18: 481-486.

Copland, D.A., Calder, C.J., Raveney, B.J.E., Nicholson, L.B., Phillips, J., Cherwinski, H., Jenmalm, M., Sedgwick, J.D., and Dick, A.D. (2007) Monoclonal antibody-mediated CD200 receptor signalling suppresses macrophage activation and tissue damage in experimental autoimmune uveoretinitis. Am. J. Pathol. 171: 580-588.

Xu, H. , Chen, M. , Mayer, E.J. , Forrester, J.V. and Dick A.D. (2007). The Turnover of Resident Retinal Microglia in the Normal Adult Mouse. Glia 55: 1189-1198.

Kemp, M.L., Wille, L., Lewis, C.L., Nicholson, L.B., and Lauffenburger, D.A. (2007) Quantitative network signal combinations downstream of TCR activation can predict IL-2 production response. J. Immunol. 178: 4984-4992.

Carter, D.A. , Mayer, E.J. , and Dick A.D. (2007). The Effect of Postmortem Time, Donor Age and Sex on the Generation of Neurospheres from Adult Human Retina. Br J Ophthalmol. 2007 91: 1216-8.


Morwood, S.R. and Nicholson, L.B. (2006) Modulation of the immune response by extracellular matrix proteins. Archivum Immunologiae et Therapiae Experimentalis 54: 1-8.

Guyver, C.J., Copland, D.A., Calder, C.J., Sette, A., Sidney, J., Dick, A.D., and Nicholson, L.B. (2006) Mapping immune responses to mRBP-3 1-16 peptide with altered peptide ligands. Invest. Ophthalmol. & Vis. Sci. 47: 2027-2035.

Nicholls, S.M. ,Banerjee, S.,Figueiredo, F.C., Crome, S., Mistry, S, Easty, D.L. , Dick, A.D. (2006). Differences in leulocyte phenotype and interferon-gamma expression in stroma and endothelium during corneal graft rejection. Exp. Eye Res. 83: 339-47.

Calder, C.J., Nicholson, L.B. and Dick, A.D. (2006) Mechanisms for inducing nasal mucosal tolerance in experimental autoimmune uveoretinitis. Methods 38: 69-76.


Calder, C.J., Nicholson, L.B., and Dick, A.D. (2005) A selective role for the TNFp55 receptor in autocrine signalling following IFN stimulation in Experimental Autoimmune Uveoretinitis (EAU). J. Immunol. 175: 6286-6293.

Taylor, N., McConnachie, K. , Calder, C.J., Dawson, R, Dick, A.D., Sedgwick, J.D. and Liversidge, J. (2005). Enhanced tolerance to autoimmune uveitis in CD200 deficient mice correlates with a pronounced Th2 switch in response to antigen challenge. J Immunol. 174: 143-154.

Broderick, C.A., Smith, A.J., Balaggan, K., Georgarias, A., Trittibach, P.C., Barker, S.E., Schlichenbrede, F.C., Bainbridge, J.W.B., Dick, A.D., and Ali, R.R. (2005). Local Administration of Adenoassociated viral vector expressing IL-10 reduces monocyte infiltration and subsequent photoreceptor damage during experimental autoimmune uveitis (EAU) Mol. Therapy 12(2):369-73.

Illes, Z., Waldner, H., Reddy, J., Bettelli, E., Nicholson, L.B. and Kuchroo, V.K. (2005) T Cell Tolerance Induced by Cross-Reactive TCR Ligands Can Be Broken by Superagonist Resulting in Anti-Inflammatory T Cell Cytokine Production, J. Immunol. 175: 1491-1497.


Reddy, J., Illes, Z., Zhang, X., Encinas, J., Pyrdol, J., Nicholson, L.B., Sobel, R.A., Wucherpfennig, K.W. and Kuchroo, V.K. (2004) Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis, PNAS 101: 15434-15439.

Anderson, A.C., Reddy, J., Nazareno, R., Sobel, R.A., Nicholson, L.B. and Kuchroo, V.K. (2004) IL-10 Plays an Important Role in the Homeostatic Regulation of the Autoreactive Repertoire in Naive Mice, J. Immunol. 173: 828-834.

Kuchroo, V.K. and Nicholson, L.B. (2003) Fast and feel good? Nature 422: 27-28.

Kuchroo, V.K., Anderson, A.C., Waldner, H., Munder, M., Bettelli, E., and Nicholson, L.B. (2002) T Cell Response in experimental autoimmune encephalomyelitis (EAE): Role of Self and Cross-Reactive Antigens in Shaping, Tuning, and Regulating the Autopathogenic T Cell Repertoire. Annu. Rev. Immunol. 20: 101-123.

Munder, M., Bettelli, E., Monney, L., Slavik, J.M., Nicholson, L.B., and Kuchroo, V.K. (2002) Reduced self-reactivity of an autoreactive T cell after activation with cross-reactive non-self ligand. J. Exp. Med. 196: 1151-1162.

Nicholson, L.B., Anderson, A.C. and Kuchroo, V.K. (2000) Tuning T cell activation threshold and effector function with cross-reactive peptide ligands. Int. Immunol. 12: 205-213.

Anderson, A.C., Nicholson, L.B., Legge, K.L., Turchin, V., Zaghouani, H. and Kuchroo, V.K. (2000) High frequency of autoreactive myelin proteolipid protein-specific T cells in the periphery of naive mice: Mechanisms of selection of the self-reactive repertoire. J. Exp. Med. 191: 761-770.

Anderson, A.C., Waldner, H.-P., Turchin, V., Jabs, C., Prabhu Das, M., Kuchroo, V.K. and Nicholson, L.B. (2000) Autoantigen responsive T cell clones demonstrate unfocused TCR cross-reactivity towards multiple related ligands: implications for autoimmunity. Cell. Immunol. 202: 88-96.

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