| | |
|
Main Navigation
|
|
Secondary Navigation
|
TRANSLATIONAL IMMUNOLOGY
Research InterestsOur research interests are focused on immune regulation in human disease. In a healthy immune system there is a balance between the pro-inflammatory responses necessary to fight infection and regulatory responses which keep these in check and maintain tolerance. Regulatory T (Treg) cells play a crucial role in maintaining peripheral tolerance, and depletion of these cells in mice results in autoimmunity. In recent years there has been much interest in Th17 cells, which are thought to play an important role in autoimmunity. The regulation of Th17 cells by Treg cells and immunomodulatory therapies is a key area of our research interest. Dysregulation of immune responses in human disease We are interested in understanding how immune responses are dysregulated in autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA). During the past few years we have investigated the regulation of Th17 cells by natural Treg cells in MS. We showed that a particular subset of Treg cells expressing the CD39 marker could suppress Th17 cells, while in contrast CD39- Treg cells actually produced IL-17. These findings highlighted an important theme in immunology, namely that considerable plasticity exists within the T helper and Treg CD4 T cell subsets. Th17 cells can convert to Th1/Th17 cells or Th17 cells, and Treg cells can switch to Th17 cells under inflammatory conditions. Furthermore, we showed that both the frequency and function of CD39+ Treg cells was impaired in MS. This research is part of a longstanding collaboration with Prof. Niall Tubridy and his team at SVUH. We are also investigating the plasticity of Treg and Th17 cells and how this might contribute to autoimmune inflammation in the RA joint. This research is in collaboration with Dr Ursula Fearon and Prof. Doug Veale at SVUH. The role of CD39+ Treg cells in colorectal cancer is also being investigated in collaboration with Dr Liz Ryan, SVUH. Immune modulation by therapies We also have a research interest in investigating the immunomodulatory effects of various therapies in MS. The role of endogenous and exogenous IFN-beta in MS is one area of interest. We have previously shown that IFN-beta exerts various immunomodulatory effects on Th17-related cytokines and specifically induced IL-27 which inhibits Th17 cells. Furthermore, the clinical response to IFN-beta treatment correlated with the induction of IL-27 by IFN-beta in vitro. These studies are ongoing and we are currently investigating possible associations of SNPs in the IL-27 gene with susceptibility to MS and response to IFN-beta treatment. A new oral immunomodulatory therapy, Fingolimod, will be available soon for the treatment of MS. Fingolimod is a sphingosine -1-phosphate antagonist which is thought to trap autoreactive T cells in the lymphoid tissues, but also has protective effects in the brain. However it has been reported that Fingolimod also specifically inhibited Th17 cells in mice. The effect of Fingolimod treatment on Th17 and Treg cells is currently being investigated. This research is in collaboration with Prof. Kumlesh Dev. It is well known that Vitamin D has a number of immunomodulatory effects, and it is used therapeutically to treat psoriasis. Furthermore, low vitamin D levels have been associated with MS and an increased risk of relapse. As part of a clinical trial to assess the effects of vitamin D supplementation in MS, we will be analyzing the effects of vitamin D supplementation on both innate and adaptive immunity. Research PersonnelSharee Basdeo (PhD Student) Collaborators Prof Niall Tubridy, Prof. Michael Hutchinson, Neurology, St. Vincent's University Hospital FundingSFI Starting Investigator Research Grant (2009-2013) Recent Publications by the Translational Immunology Group |
|
Contact: bbutler@tcd.ie. |
Last updated: Feb 22 2012.
|
