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Trinity College Dublin, The University of Dublin

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Dr. Jean Fletcher
Associate Prof in Translational Immunolo, Biochemistry
Associate Prof in Translational Immunolo, Clinical Medicine

Publications and Further Research Outputs

Peer-Reviewed Publications

MacMahon Copas AN, McComish SF, Petrasca A, McCormack R, Ivers D, Stricker A, Fletcher JM, Caldwell MA., CD4+ T cell-associated cytokines induce a chronic pro-inflammatory phenotype in induced pluripotent stem cell-derived midbrain astrocytes., Glia, 2024 Journal Article, 2024 DOI

Leacy EJ, Teh JW, O'Rourke AM, Brady G, Gargan S, Conlon N, Scott J, Dunne J, Phelan T, Griffin MD, Power J, Mooney A, Naughton A, Kiersey R, Gardiner M, O'Brien C, Mullan R, Flood R, Clarkson M, Townsend L, O'Shaughnessy M, Dyer AH, Moran B, Fletcher JM, Zgaga L, Little MA, RITA Ireland Vasculitis Biobank., Effect of Immunosuppression on the Immune Response to SARS-CoV-2 Infection and Vaccination., International journal of molecular sciences, 25, (10), 2024, p5239 Journal Article, 2024 DOI

Campbell C, Mayatra JM, Neve AJ, Fletcher JM, Johnston DGW., Inflammasomes: emerging therapeutic targets in hidradenitis suppurativa?, The British journal of dermatology, 2024, pljae262 Review Article, 2024 DOI

Petrasca A, Hambly R, Kearney N, Smith CM, Pender EK, Mac Mahon J, O'Rourke AM, Ismaiel M, Boland PA, Almeida JP, Kennedy C, Zaborowski A, Murphy S, Winter D, Kirby B, Fletcher JM., Metformin has anti-inflammatory effects and induces immunometabolic reprogramming via multiple mechanisms in hidradenitis suppurativa., The British journal of dermatology, 189, (6), 2023, p730-740 Journal Article, 2023 DOI

Hambly R, Kearney N, Hughes R, Fletcher JM, Kirby B., Metformin Treatment of Hidradenitis Suppurativa: Effect on Metabolic Parameters, Inflammation, Cardiovascular Risk Biomarkers, and Immune Mediators., International journal of molecular sciences, 24, (8), 2023, p6969 Journal Article, 2023 DOI

Petrasca A, Hambly R, Molloy O, Kearns S, Moran B, Smith CM, Hughes R, O'Donnell M, Zaborowski A, Winter D, Fletcher JM, Kirby B, Malara A., Innate lymphoid cell (ILC) subsets are enriched in the skin of patients with hidradenitis suppurativa., PloS one, 18, (2), 2023, pe0281688 Journal Article, 2023 DOI

Gaynor N, Blanco A, Madden SF, Moran B, Fletcher JM, Kaukonen D, Ramírez JS, Eustace AJ, McDermott MSJ, Canonici A, Toomey S, Teiserskiene A, Hennessy BT, O'Donovan N, Crown J, Collins DM., Alterations in immune cell phenotype and cytotoxic capacity in HER2+ breast cancer patients receiving HER2-targeted neo-adjuvant therapy., British journal of cancer, 129, (6), 2023, p1022-1031 Journal Article, 2023 DOI

O'Connor, C., Jordan, K., Vagg, T., Murphy, C.E., Barry, D.B., Toulouse, A., Flecther, J., Downer, E.J., Animated teaching improves student learning of human gastrulation and neurulation., Annals of Anatomy, in press, 2023 Journal Article, 2023 URL DOI

Barker BE, Hanlon MM, Marzaioli V, Smith CM, Cunningham CC, Fletcher JM, Veale DJ, Fearon U, Canavan M., The mammalian target of rapamycin contributes to synovial fibroblast pathogenicity in rheumatoid arthritis., Frontiers in medicine, 10, 2023, p1029021 Journal Article, 2023 DOI

Hambly R, Gatault S, Smith CM, Iglesias-Martinez LF, Kearns S, Rea H, Marasigan V, Lynam-Loane K, Kirthi S, Hughes R, Fletcher JM, Kolch W, Kirby B., B-cell and complement signature in severe hidradenitis suppurativa that does not respond to adalimumab., The British journal of dermatology, 188, (1), 2023, p52-63 Journal Article, 2023 DOI

Smith CM, Hambly R, Gatault S, Iglesias-Martinez LF, Kearns S, Rea H, Marasigan V, Lynam-Loane K, Kirthi S, Hughes R, Fletcher JM, Kolch W, Kirby B., B-cell-derived transforming growth factor-ß may drive the activation of inflammatory macrophages and contribute to scarring in hidradenitis suppurativa., The British journal of dermatology, 188, (2), 2023, p290-310 Journal Article, 2023 DOI

Moran, B. and Smith, C.M. and Zaborowski, A. and Ryan, M. and Karman, J. and Dunstan, R.W. and Smith, K.M. and Hambly, R. and Musilova, J. and Petrasca, A. and Fabre, A. and O'Donnell, M. and Hokamp, K. and Mills, K.H.G. and Housley, W.J. and Winter, D.C. and Kirby, B. and Fletcher, J.M., Targeting the NLRP3 inflammasome reduces inflammation in hidradenitis suppurativa skin, The British journal of dermatology, 189, (4), 2023, p447-458 Journal Article, 2023 DOI

Floudas A, Smith CM, Tynan O, Neto N, Krishna V, Wade SM, Hanlon M, Cunningham C, Marzaioli V, Canavan M, Fletcher JM, Mullan RH, Cole S, Hao LY, Monaghan MG, Nagpal S, Veale DJ, Fearon U., Distinct stromal and immune cell interactions shape the pathogenesis of rheumatoid and psoriatic arthritis., Annals of the rheumatic diseases, 2022, pannrheumdis-2021-221761 Journal Article, 2022 DOI

Fitzgerald, H.K.; O'Rourke, S.A.; Desmond, E.; Neto, N.G.B.; Monaghan, M.G.; Tosetto, M.; Doherty, J.; Ryan, E.J.; Doherty, G.A.; Nolan, D.P.; Fletcher, J.M.; Dunne, A, The Trypanosoma brucei-Derived Ketoacids, Indole Pyruvate and Hydroxyphenylpyruvate, Induce HO-1 Expression and Suppress Inflammatory Responses in Human Dendritic Cells, Antioxidants, 11, 2022, p164- Journal Article, 2022 DOI

MacMahon Copas AN, McComish SF, Fletcher JM, Caldwell MA., The Pathogenesis of Parkinson's Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes?, Frontiers in neurology, 12, 2021, p666737 Review Article, 2021 DOI

Kirby B, Fletcher JM., Mechanism of action of dimethyl fumarate: a small molecule with big effects., The British journal of dermatology, 185, (3), 2021, p483-484 Journal Article, 2021 DOI

Petrasca A, Phelan J.J., Ansboro S, Veale D.J., Fearon U., Fletcher J.M., Targeting bioenergetics prevents CD4 T cell-mediated activation of synovial fibroblasts in rheumatoid arthritis., Rheumatology, 2020 Journal Article, 2020 URL DOI

Fletcher JM, Moran B, Petrasca A, Smith CM., IL-17 in inflammatory skin diseases psoriasis and hidradenitis suppurativa., Clinical and experimental immunology, 201, (2), 2020, p121-134 Review Article, 2020 DOI

Sulaimani J, Cluxton D, Clowry J, Petrasca A, Molloy OE, Moran B, Sweeney CM, Malara A, McNicholas N, McGuigan C, Kirby B, Fletcher JM., Dimethyl fumarate modulates the Treg-Th17 cell axis in patients with psoriasis., The British journal of dermatology, 2020 Journal Article, 2020 DOI

Cluxton D, Petrasca A, Moran B, Fletcher JM, Differential regulation of human Treg and Th17 cells by fatty acid synthesis and glycolysis, Frontiers in Immunology, 10, 2019, p115- Journal Article, 2019 TARA - Full Text DOI

J. Musilova, B. Moran, C.M. Sweeney, A. Malara, A. Zaborowski, R. Hughes, D.C. Winter, J.M. Fletcher, B. Kirby, Enrichment of Plasma Cells in the Peripheral Blood and Skin of Patients with Hidradenitis Suppurativa, Journal of Investigative Dermatology, 2019 Journal Article, 2019 DOI

Campbell, N.K. and Fitzgerald, H.K. and Fletcher, J.M. and Dunne, A., Plant-derived polyphenols modulate human dendritic cell metabolism and immune function via AMPK-dependent induction of heme oxygenase-1, Frontiers in Immunology, 10, (MAR), 2019, p00345- Journal Article, 2019 DOI TARA - Full Text

Moran B, Gallagher C, Tobin AM, Fletcher JM., Enrichment of polyfunctional IL-17 producing T cells in paradoxical psoriasis skin lesions., The Journal of investigative dermatology, 2019 Journal Article, 2019 DOI

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 - Journal Article, 2018 TARA - Full Text 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, 2018 DOI TARA - Full Text

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, 2018 DOI

O'Connell K, Sulaimani J, Basdeo SA, Kinsella K, Jordan S, Kenny O, Kelly SB, Murphy D, Heffernan E, Killeen RP, Mulready K, MacMahon M, Brady JJ, McKenna C, Muldowney C, Cassidy L, Walsh C, O'Rourke K, Tubridy N, McGuigan C, Fletcher JM, Hutchinson M., Effects of vitamin D3 in clinically isolated syndrome and healthy control participants: A double-blind randomised controlled trial., Multiple sclerosis journal - experimental, translational and clinical, 3, (3), 2017, p2055217317727296 Journal Article, 2017 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, 2017 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, 2017 DOI

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, 2016 TARA - Full Text DOI URL

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, 2016 DOI 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, 2016 TARA - Full Text DOI URL

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, 2016 DOI

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, 2015 DOI

Kelly, A., Fahey, R., Fletcher, J.M., Keogh, C., Carroll, A.G., Siddachari, R., Geoghegan, J., Hegarty, J.E., Ryan, E.J., O'Farrelly, C., CD141+ myeloid dendritic cells are enriched in healthy human liver, Journal of Hepatology, 60, (1), 2014, p135-142 Journal Article, 2014 DOI

Fletcher, J., Hutchinson, M., Tubridy, N., Response to comment on the article by Allen et al. 'A pilot study of the immunological effects of high-dose vitamin D in healthy volunteers', Multiple Sclerosis , 19, (4), 2013, p509 Journal Article, 2013 DOI

O'Connell K, Kelly S, Kinsella K, Jordan S, Kenny O, Murphy D, Heffernan E, O'Laoide R, O'Shea D, McKenna C, Cassidy L, Fletcher J, Walsh C, Brady J, McGuigan C, Tubridy N, Hutchinson M, Dose-related effects of vitamin D on immune responses in patients with clinically isolated syndrome and healthy control participants: study protocol for an exploratory randomized double- blind placebo-controlled trial., Trials, 14, 2013, p272 Journal Article, 2013 DOI TARA - Full Text

Jean M Fletcher, Sharee A Basdeo, Aideen C Allen and Padraic J Dunne, Therapeutic use of vitamin D and its analogues in autoimmunity, Recent Patents in Inflammation Allergy Drug Discovery, 6, (1), 2012, p22 - 34 Review Article, 2012 DOI

Immunology of Multiple Sclerosis in, The Biology of Multiple Sclerosis, Cambridge University Press, 2012, pp1-146 , [Fletcher JM and Mills KHG] Book Chapter, 2012 DOI URL

Allen AC, Kelly S, Basdeo SA, Kinsella K, Mulready KJ, Mills KH, Tubridy N, Walsh C, Brady JJ, Hutchinson M, Fletcher JM, A pilot study of the immunological effects of high-dose vitamin D in healthy volunteers., Multiple sclerosis (Houndmills, Basingstoke, England), 18, (12), 2012, p1797 - 1800 Journal Article, 2012 DOI

Cheryl M. Sweeney, Roisin Lonergan, Sharee A. Basdeo, Katie Kinsella, Lara S. Dungan, Sarah C. Higgins, Patrick J. Kelly, Lisa Costelloe, Niall Tubridy, Kingston H.G. Mills, Jean M. Fletcher, IL-27 mediates the response to IFN beta therapy in multiple sclerosis patients by inhibiting Th17 cells, Brain, Behavior and Immunity, 25, (6), 2011, p1170-1181 Journal Article, 2011 TARA - Full Text

Lalor, S.J., Dungan, L.S., Sutton, C.E., Basdeo, S.A., Fletcher, J.M., Mills, K.H.G., Caspase-1-processed cytokines IL-1β and IL-18 promote IL-17 production by γδ and CD4 T cells that mediate autoimmunity, Journal of Immunology, 186, (10), 2011, p5738-5748 Journal Article, 2011 DOI

O'Brien M, Lonergan R, Costelloe L, O'Rourke K, Fletcher JM, Kinsella K, Sweeney C, Antonelli G, Mills KH, O'Farrelly C, Hutchinson M, Tubridy N. , OAS1: a multiple sclerosis susceptibility gene that influences disease severity., Neurology, 75, (5), 2010, p411 - 418 Journal Article, 2010 DOI

Hoare M, Gelson WT, Das A, Fletcher JM, Davies SE, Curran MD, Vowler SL, Maini MK, Akbar AN, Alexander GJ., CD4+ T-lymphocyte telomere length is related to fibrosis stage, clinical outcome and treatment response in chronic hepatitis C virus infection., Journal of Hepatology, 53, (2), 2010, p252 - 260 Journal Article, 2010 TARA - Full Text

Fletcher, J.M., Lalor, S.J., Sweeney, C.M., Tubridy, N., Mills, K.H.G, T cells in multiple sclerosis and experimental autoimmune encephalomyelitis , Clinical and Experimental Immunology, 162, (1), 2010, p1-11 Review Article, 2010 TARA - Full Text

Fletcher JM, Lonergan R, Costelloe L, Kinsella K, Moran B, O'Farrelly C, Tubridy N, Mills KH, CD39+Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis., Journal of Immunology , 183, (11), 2009, p7602-7610 Journal Article, 2009 TARA - Full Text DOI

Jarnicki, AJ, Conroy, H. Brereton, C, Donnelly, G., Toomey, D., Walsh, K.,, Sweeney, C., Leavy, O., Fletcher, J., Lavelle, E., Dunne, P. and Mills, K.H.G., Attenuating regulatory T cell induction by TLR agonists through inhibition of p38 MAPK signaling in dendritic cells enhances their efficacy as vaccine adjuvants and cancer immunotherapeutics, Journal of Immunology, 180, (6), 2008, p3797 - 3806 Journal Article, 2008 DOI TARA - Full Text URL

Rowan AG, Fletcher JM, Ryan EJ, Moran B, Hegarty JE, O'Farrelly C and Mills KHG, Hepatitis C virus-specific Th17 cells are suppressed by virus-induced TGF-beta, Journal of Immunology, 181, (7), 2008, p4485 - 4494 Journal Article, 2008 TARA - Full Text URL DOI

Van Baarle, D., Nanlohy, N.M., Otto, S., Plunkett, F.J., Fletcher, J.M., Akbar, A.N., Progressive telomere shortening of Epstein-Barr virus-specific memory T cells during HIV infection: Contributor to exhaustion, Journal of Infectious Diseases, 198, (9), 2008, p1353-1357 Journal Article, 2008 DOI

IL-10 and TGF-beta-producing regulatory T cells in infection in, editor(s)Shuiping Jiang , Regulatory cells and Clinical Application, Springer Science and Business Media, LLC , 2008, pp423 - 453, [Dunne PJ, Rowan A, Fletcher JM and KHG Mills] Book Chapter, 2008 DOI

Colonna-Romano G, Akbar AN, Aquino A, Bulati M, Candore G, Lio D, Ammatuna P, Fletcher JM, Caruso C, Pawelec G. , Impact of CMV and EBV seropositivity on CD8 T lymphocytes in an old population from West-Sicily., Experimental Gerontology, 42, (10), 2007, p995-1002. Journal Article, 2007 DOI

Plunkett FJ, Franzese O, Finney HM, Fletcher JM, Belaramani LL, Salmon M, Dokal I, Webster D, Lawson AD, Akbar AN., The loss of telomerase activity in highly differentiated CD8+CD28-CD27- T cells is associated with decreased Akt (Ser473) phosphorylation., Journal of Immunology , 178, (12), 2007, p7710-7719 Journal Article, 2007 DOI URL

Vukmanovic-Stejic M, Zhang Y, Cook JE, Fletcher JM, McQuaid A, Masters JE, Rustin MH, Taams LS, Beverley PC, Macallan DC, Akbar AN., Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo., Journal of Clinical Investigation, 116, (9), 2006, p2423-2433. Journal Article, 2006 DOI

Akbar AN, Fletcher JM., Memory T cell homeostasis and senescence during aging., Current Opinion in Immunology, 17, (5), 2005, p480-485 Review Article, 2005 DOI

Dunne PJ, Belaramani L, Fletcher JM, Fernandez de Mattos S, Lawrenz M, Soares MV, Rustin MH, Lam EW, Salmon M, Akbar AN, Quiescence and functional reprogramming of Epstein-Barr virus (EBV)-specific CD8+ T cells during persistent infection. , Blood, 106, (2), 2005, p558-565 Journal Article, 2005 DOI

Fletcher JM, Vukmanovic-Stejic M, Dunne PJ, Birch KE, Cook JE, Jackson SE, Salmon M, Rustin MH, Akbar AN., Cytomegalovirus-specific CD4+ T cells in healthy carriers are continuously driven to replicative exhaustion., Journal of Immunology , 175, (12), 2005, p8218-8225 Journal Article, 2005 URL DOI

Plunkett FJ, Franzese O, Belaramani LL, Fletcher JM, Gilmour KC, Sharifi R, Khan N, Hislop AD, Cara A, Salmon M, Gaspar HB, Rustin MH, Webster D, Akbar AN. , The impact of telomere erosion on memory CD8+ T cells in patients with X-linked lymphoproliferative syndrome., Mechanisms of Ageing and Development, 126, (8), 2005, p855-865 Journal Article, 2005 DOI

Reed JR, Vukmanovic-Stejic M, Fletcher JM, Soares MV, Cook JE, Orteu CH, Jackson SE, Birch KE, Foster GR, Salmon M, Beverley PC, Rustin MH, Akbar AN. , Telomere erosion in memory T cells induced by telomerase inhibition at the site of antigenic challenge in vivo., Journal of Experimental Medicine, 199, (10), 2004, p1433-1443 Journal Article, 2004 DOI

Soares MV, Plunkett FJ, Verbeke CS, Cook JE, Faint JM, Belaramani LL, Fletcher JM, Hammerschmitt N, Rustin M, Bergler W, Beverley PC, Salmon M, Akbar AN., Integration of apoptosis and telomere erosion in virus-specific CD8+ T cells from blood and tonsils during primary infection., Blood., 103, (1), 2004, p162-167 Journal Article, 2004 DOI

Lantto J, Fletcher JM, Ohlin M., Binding characteristics determine the neutralizing potential of antibody fragments specific for antigenic domain 2 on glycoprotein B of human cytomegalovirus, Virology., 305, (1), 2003, p201-209 Journal Article, 2003 DOI

Taams, L.S., Vukmanovic-Stejic, M., Smith, J., Dunne, P.J., Fletcher, J.M., Plunkett, F.J., Ebeling, S.B., (...), Akbar, A.N., 17. Taams LS, Vukmanovic-Stejic M, Smith J, Dunne PJ, Fletcher JM, Plunkett FJ, Ebeling SB, Lombardi G, Rustin MH, Bijlsma JW, Lafeber FP, Salmon M, Akbar AN. Antigen-specific T cell suppression by human CD4+CD25+ regulatory T cells., European Journal of Immunology, 32, (6), 2002, p1621-1630 Journal Article, 2002 DOI

Dunne PJ, Faint JM, Gudgeon NH, Fletcher JM, Plunkett FJ, Soares MV, Hislop AD, Annels NE, Rickinson AB, Salmon M, Akbar AN., Epstein-Barr virus-specific CD8(+) T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential., Blood, 100, (3), 2002, p933-940. Journal Article, 2002 DOI

*Lantto J, *Fletcher JM, Ohlin M. , A divalent antibody format is required for neutralization of human cytomegalovirus via antigenic domain 2 on glycoprotein B, Journal of General Virology, 83, (8), 2002, p2001-2005 Journal Article, 2002 DOI URL

Marais, G.I., Fletcher, J.M., Potter, P.C., In vivo and in vitro diagnosis of latex allergy at Groote Schuur Hospital , Ugeskrift for Laeger , 161, (29), 1999, p1004-1008 Journal Article, 1999

Fletcher JM, Prentice HG, Grundy JE., Natural killer cell lysis of cytomegalovirus (CMV)-infected cells correlates with virally induced changes in cell surface lymphocyte function-associated antigen-3 (LFA-3) expression and not with the CMV-induced down-regulation of cell surface class I HLA. , Journal of Immunology, 161, (5), 1998, p2365-2374 Journal Article, 1998 DOI URL

Grundy JE, Lawson KM, MacCormac LP, Fletcher JM, Yong KL., Cytomegalovirus-infected endothelial cells recruit neutrophils by the secretion of C-X-C chemokines and transmit virus by direct neutrophil-endothelial cell contact and during neutrophil transendothelial migration, Journal of Infectious Diseases, 177, (6), 1998, p1465-1474. Journal Article, 1998 DOI

Non-Peer-Reviewed Publications

Corrigan M, O'Rourke AM, Moran B, Fletcher JM, Harkin A., Inflammation in the pathogenesis of depression: a disorder of neuroimmune origin., Neuronal Signal, 7, (2), 2023, pNS20220054- Review Article, 2023 DOI

Research Expertise

Description

Th17 cells are key players in autoimmune/inflammatory diseases and an important therapeutic target. My independent research career has focused on understanding the regulation of Th17 cells in human diseases. 20/65 articles have been cited >100 times, indicating the significant impact of my research. I have established clinical collaborations which have underpinned the translational aspects of my work. My overarching research aim is to understand the role of Th17 cells in human disease and how they can be targeted therapeutically. My early work into the role of Th17 cells in MS made a significant impact by dissecting the regulation of IL-17 by different types of regulatory T (Treg) cells and demonstrated defective regulation in MS patients. Subsequent work showed how pathogenic Th17 cells in MS patients were inhibited by IFN-ß therapy. Our research into Th17 cells in RA demonstrated that Th17 cells in the RA joint are highly inflammatory and resistant to regulation. Th17 cells were unstable and switched into a highly pathogenic ex-Th17 phenotype, potentially explaining the lack of success of anti-IL-17 therapies in RA. We demonstrated differential regulation of Th17 vs Treg cells by metabolic pathways, allowing for therapeutic manipulation. We also showed that T cells induced a switch towards glycolysis in RA synovial fibroblasts and that targeting glycolysis could reverse these inflammatory effects. More recently, our research into HS revealed several therapeutic targets which can reduce inflammation in HS. We identified Th17 cells as a key target, and indeed the first anti-IL-17A drug was recently licensed for HS. We showed that inflammation/Th17 cells in HS could be targeted using metformin and inhibitors of the NLRP3 inflammasome. Given that metformin is a cheap drug and inflammasome inhibitors are currently in clinical development, these findings are significant as HS is a disease with a high unmet need for effective therapies.

Projects

  • Title
    • Dysregulation of pathogenic T cells in multiple sclerosis
  • Funding Agency
    • HRB
  • Date From
    • 2006
  • Date To
    • 2009
  • Title
    • The role of CD39+ regulatory T cells in autoimmune disease
  • Funding Agency
    • SFI
  • Date From
    • 2009
  • Date To
    • 2014

Keywords

Autoimmune Diseases (Multiple Sclerosis, Rheumatoid Arthritis); Autoimmunity; HIDRADENITIS SUPPURATIVA; 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

Recognition

Representations

External examiner for UCL: I was invited to act as external examiner for the MSc and MRes in Experimental Translational Immunology at UCL due to my extensive experience in translational immunology research and research led teaching . This role involves reviewing exam papers and research projects, attending Board of Examiner meetings and providing recommendations for the course and an annual report. 2022

Scientific advisor for H-Strong biobank: I was invited to as as scientific advisor for this UK based biobank of samples from HS patients due to my expertise in HS research and sample collection. 2023

External examiner for PhD (PhD candidate Ushani Srenathan, King"s College London) I was invited as external examiner for this PhD viva due to my expertise in T cell immunology and rheumatoid arthritis 28-Nov-2018

External examiner for PhD (PhD candidate Andrea Iannello, University of Turin, Turin, Italy. I was invited as external examiner for this candidate due to my expertise in multiple sclerosis research. 17-Dec-2018

Awards and Honours

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

Fellow of Trinity College Dublin 2021

Memberships

British Society for Immunology 2000 – present

Irish Society for Immunology 2005 – present

Biochemical Society 2005 – present