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Dr. Jean Fletcher

Ussher Ast Prof Translational Immunology (Biochemistry)

Ussher Ast Prof Translational Immunology (Clinical Medicine)


  Autoimmune Diseases (Multiple Sclerosis, Rheumatoid Arthritis)   Autoimmunity   IMMUNE FUNCTION   Immune regulation   Immune system   IMMUNE-RESPONSE   IMMUNITY   Immunoassays   IMMUNOLOGICAL MECHANISMS   IMMUNOLOGICAL REGULATION   Immunology   Immunology, Immunotherapy   Immunotherapy   Multiple Sclerosis   MULTIPLE-SCLEROSIS   Regulatory T cells   Rheumatology and rheumatological disorders   T cells   Th17 cells   Tumour Biology/ Immunology
 Dysregulation of pathogenic T cells in multiple sclerosis
 The role of CD39+ regulatory T cells in autoimmune disease

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Details Date From Date To
British Society for Immunology 2000 present
Irish Society for Immunology 2005 present
Biochemical Society 2005 present
Campbell, N.K. and Fitzgerald, H.K. and Malara, A. and Hambly, R. and Sweeney, C.M. and Kirby, B. and Fletcher, J.M. and Dunne, A., Naturally derived Heme-Oxygenase 1 inducers attenuate inflammatory responses in human dendritic cells and T cells: Relevance for psoriasis treatment, Scientific Reports, 8, (1), 2018, p10287 -, Notes: [cited By 0], Journal Article, PUBLISHED  TARA - Full Text  DOI
O'Rourke M, Fearon U, Sweeney CM, Basdeo SA, Fletcher JM, Murphy CC, Canavan M, The pathogenic role of dendritic cells in non-infectious anterior uveitis., Experimental eye research, 2018, p121 - 128, Journal Article, PUBLISHED  DOI
Canavan M, Walsh AM, Bhargava V, Wade SM, McGarry T, Marzaioli V, Moran B, Biniecka M, Convery H, Wade S, Orr C, Mullan R, Fletcher JM, Nagpal S, Veale DJ, Fearon U, Enriched CD141+ DCs in the joint are transcriptionally distinct, activated, and contribute to joint pathogenesis., JCI Insight, 3, (23), 2018, p95228-, Journal Article, PUBLISHED  DOI
Sharee A. Basdeo, Deborah Cluxton, Jamal Sulaimani, Barry Moran, Mary Canavan, Carl Orr, Douglas J. Veale, Ursula Fearon and Jean M. Fletcher, Ex-Th17 (Nonclassical Th1) Cells Are Functionally Distinct from Classical Th1 and Th17 Cells and Are Not Constrained by Regulatory T Cells., J immunology, 198 , (2), 2017, p2249 - 2259, Journal Article, PUBLISHED  DOI
Barry Moran, Cheryl M. Sweeney, Rosalind Hughes, Anna Malara, Shivashini Kirthi, Anne-Marie Tobin, Brian Kirby, Jean M. Fletcher, Hidradenitis Suppurativa Is Characterized by Dysregulation of the Th17:Treg Cell Axis, Which Is Corrected by Anti-TNF Therapy, Journal of Investigative Dermatology, 137, (11), 2017, p2389--2395 , Journal Article, PUBLISHED  DOI
Neuroinflammatory Disorders in, editor(s)Orla Hardiman, Colin P. Doherty, Marwa Elami, Peter Bede , Neurodegenerative Disorders, Springer International Publishing, 2016, pp269 - 287, [Costelloe C, Fletcher JM, Fitzgerald D. Neuroinflammatory Disorders. (In Neurodegenerative Disorders).], Book Chapter, PUBLISHED
Dunne M, Ryan C, Tosetto M, Nolan B, Geraghty R, Winter DC, O'Connell R, Hyland J, Doherty GA, Sheahan K, Ryan EJ, Fletcher JM., Enrichment of inflammatory IL-17 and TNF-α secreting CD4+ T cells within colorectal tumours despite the presence of elevated CD39+ T regulatory cells and increased expression of the immune checkpoint molecule, PD-1., Frontiers in Oncology, 6, 2016, p50-, Journal Article, PUBLISHED  TARA - Full Text  URL
Basdeo SA, Kelly S, O'Connell K, Tubridy N, McGuigan C, Fletcher JM, Increased expression of Tbet in CD4+ T cells from clinically isolated syndrome patients at high risk of conversion to clinically definite MS. , Springer Plus, 5, 2016, p779-, Journal Article, PUBLISHED  TARA - Full Text  URL
Basdeo S.A, Campbell N.K, Sullivan L.M, Flood B, Creagh E.M, Mantle T.J, Fletcher J.M, Dunne A, Suppression of human alloreactive T cells by linear tetrapyrroles; relevance for transplantation, Translational Research, 178, 2016, p81-94.e2 , Journal Article, PUBLISHED  TARA - Full Text  DOI  URL
Basdeo, S.A., Moran, B., Cluxton, D., (...), Fearon, U., Fletcher, J.M., Polyfunctional, pathogenic CD161+ Th17 lineage cells are resistant to regulatory T cell-mediated suppression in the context of autoimmunity, Journal of Immunology, 195, (2), 2015, p528-540 , Journal Article, PUBLISHED  DOI
  

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Award Date
First prize for the best oral presentation at the Irish Society for Immunology 2008 Annual Congress. 2008
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. 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. 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. 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.