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Professor Hill Gaston

Professor Hill Gaston

Hill Gaston is accepting applications for PhD students.

Hill Gaston is available for consultancy.


Departments

Department of Medicine:
Professor of Rheumatology

Research Interests

My lab is interested in the pathogenesis of inflammatory arthritis with particular emphasis on HLA-B27 associated spondyloarthritis (SpA) and the role of T cells. As well as the association with HLA-B27, recent genetic evidence strongly implicates the Th17/IL-23 pathway in disease.Th17 cells are increased in SpA especially in affected joints. We previously shown high numbers of bacteria-specific T cells in reactive arthritis joints, but the bacterial epitopes recognized are not conserved in human proteins - i.e. molecular mimicry was not demonstrated. We pursued the idea that expression of B27 alters dendritic cell function, via ER stress pathways. We have shown that ER stress greatly favours IL-23 production over IL-12 in a mechanism depending on the transcription factor CHOP. B27 expression alone does not initiate ER stress but intracellular infection with SpA-associated bacteria does. We are now determining how signals from pathogens through PRRs interact with stress responses to affect cytokine production, particularly IL-23, but also we have begun work on TSLP whose production also seems to be affected by ER stress. We are also characterizing T cell subsets in blood, joints (and skin in patients with psoriasis and arthritis) in terms of surface phenotype and production of cytokines such as IL-17, IL-22, GM-CSF and IFNγ.
 
We have a longstanding interest in regulatory T cells, initially an unusual CD8+ subset which appeared expanded in patients with B27-associated arthritis. More recently we have been working on CD4+ regulatory T cells, defining subtypes, and estimating their prevalence and function in arthritis.

Keywords

FOXP3 ; autoimmunity ; helper T cells ; T cells ; CD8+ ; CD4+ ; interleukin

Topics

  • arthritis
  • inflammatory arthritis

Key Publications

Prevosto C, Goodall JC, and Gaston JSH. Cytokine secretion by Pathogen Recognition Receptor-stimulated dendritic cells in rheumatoid arthritis and ankylosing spondylitis. J. Rheumatol. 2012 In Press.

Goodall JC, Wu C, Zhang Y, Ellis L, O’Brien L, Saudek V, and Gaston JSH, ER stress signals are integrated by dendritic cells to enhance IL-23 responses to Toll-like receptor. PNAS (USA) 2010 107: (41) 17698–17703.
 
Kaur G, Goodall JC, Jarvis LB, Gaston JSH. Characterisation of Foxp3 Splice Variants in human CD4+ and CD8+ T cells - Identification of Foxp3Δ7 in human regulatory T cells. Molecular Immunology 2010 48:321–332
 
Soond DR, Bjorgo E, Moltu K, Dale VQ, Patton DT, Torgersen KM, Galleway F, Twomey B, Clark J, Gaston JSH, Tasken K, Bunyard, P, and Okkenberg K. PI3Kp110d regulates T cell cytokine production during primary and secondary immune responses in mice and humans. Blood 2010 115:2203–2213
 
Shen H, Goodall J, and Gaston JSH. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum 2009 60:1647–1656
 
Jarvis LB, Goodall JC, Gaston JSH. Human leukocyte antigen class I-restricted immunosuppression by human CD8+ regulatory T cells requires CTLA-4 mediated interaction with dendritic cells. Human Immunology 2008 69:687–695