Inflammation and inflammatory disease; Immune regulation
Uveitis (intraocular inflammation)
The eye is normally protected from the harmful side-effects of immune responses. However, for patients with uveitis this degree of protection appears to have failed and they can develop sight-threatening inflammation. Our research aims to determine how inflammation in the eye of patients with uveitis is regulated. We are currently studying the role of both aggressive and regulatory T cell subsets in this disease. This work is in collaboration with the clinicians in the unit, Prof Phil Murray and Dr Alastair Denniston.
T cell differentiation
Central to our understanding of autoimmune and inflammatory diseases, is our knowledge of how the relevant lymphocyte subsets differentiate in a healthy context. There are a wide variety of different types of lymphocyte. Our current projects are attempting to characterise these cells in more detail from the blood of healthy volunteer donors. We are examining the features of the cells, how they function and what controls their differentiation.
The central nervous system, like the eye, is relatively protected from damaging inflammation. However in patients with multiple sclerosis there is a destructive inflammatory process with many pathogenic lymphocytes entering the central nervous system. We are currently studying these cells to determine which cells are specific to this disease and how they relate to the clinical progression. This work is in collaboration with consultant neurologists at the QE Hospital Birmingham.
Denniston AK, Tomlins PJ, Williams GP, Kottoor S, Khan IJ, Oswal K, Salmon M, Wallace GR, Rauz S, Dr. Murray PI, Curnow SJ. (2012), Aqueous humor suppression of dendritic cell function helps maintain immune regulation in the eye during human uveitis. Invest. Ophthal. Vis. Sci. In press
Williams GP, Denniston AK, Oswal KS, Tomlins PJ, Barry RJ, Rauz S, Curnow SJ. (2011), The dominant human conjunctival epithelial CD8αβ+ T cell population is maintained with age but the number of CD4+ T cells increases. Age. [Epub ahead of print].
Hidalgo E, Essex SJ, Yeo L, Curnow SJ, Filer A, Cooper MS, Thomas AM, McGettrick HM, Salmon M, Buckley CD, Raza K, Scheel-Toellner D. (2011), The response of T cells to interleukin-6 is differentially regulated by the microenvironment of the rheumatoid synovial fluid and tissue. Arthritis Rheum. 63:3284-93.
Turan N, Kalko S, Stincone A, Clarke K, Sabah A, Howlett K, Curnow SJ, Rodriguez DA, Cascante M, O'Neill L, Egginton S, Roca J, Falciani F. (2011), A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease. PLoS Comput Biol. Epub Sep 1.
Hardie DL, Baldwin MJ, Naylor A, Haworth OJ, Hou TZ, Lax S, Curnow SJ, Willcox N, MacFadyen J, Isacke CM, Buckley CD. (2011), The stromal cell antigen CD248 (endosialin) is expressed on naive CD8+ human T cells and regulates proliferation. Immunology. 133:288-95.
Denniston AK, Kottoor SH, Khan I, Oswal K, Williams GP, Abbott J, Wallace GR, Salmon M, Rauz S, Murray PI, Curnow SJ. (2011), Endogenous cortisol and TGF-beta in human aqueous humor contribute to ocular immune privilege by regulating dendritic cell function. J Immunol. 186:305-11.
Williams GP, Saw VP, Saeed T, Evans ST, Cottrell P, Curnow SJ, Nightingale P, Rauz S. (2010), Validation of a fornix depth measurer: a putative tool for the assessment of progressive cicatrising conjunctivitis. Br J Ophthalmol. [Epub ahead of print]
Curnow SJ, Fairclough M, Schmutz C, Kissane S, Denniston AKO, Nash K, Buckley CD, Lord JM, Salmon M. (2010), Distinct types of fibrocyte can differentiate from mononuclear cells in the presence and absence of serum. PLoS One. 2010 5:e9730.
Whitehead KJ, Smith CG, Delaney SA, Curnow SJ, Salmon M, Hughes JP, Chessell IP. (2010), Dynamic regulation of spinal pro-inflammatory cytokine release in the rat in vivo following peripheral nerve injury. Brain Behav Immun. 24(4):569-76.
Agius E, Lacy KE, Vukmanovic-Stejic M, Jagger AL, Papageorgiou AP, Hall S, Reed JR, Curnow SJ, Fuentes-Duculan J, Buckley CD, Salmon M, Taams LS, Krueger J, Greenwood J, Klein N, Rustin MH, Akbar AN. (2009), Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging. J. Exp. Med.