Team Science targeting the immune system to repair the brain
The central goal of our research is to identify new strategies to treat MS and other inflammatory and demyelinating conditions. We are particularly interested in the process of myelin repair (remyelination) and aim to identify novel therapeutic targets to promote remyelination in MS. This regenerative medicine research programme is supported by a range of collaborators internationally.
Understanding inflammatory damage in the Central Nervous System
We also conduct a research programme on the pathogenesis of autoimmune inflammation. This programme mainly focuses on T cell biology with a view to identifying strategies to reduce disease activity in MS and other immune-mediated diseases.
Our hard-working team consists of members from the fields of Neuroscience, Immunology and Regenerative biology who work together to study neuro-immune cellular communication and interaction with stem cells. We hope to gain new insights into the influence of the immune system and inflammation on demyelination and remyelination in the CNS.
Publications
2023
Ageing impairs the regenerative capacity of regulatory T cells in central nervous system remyelination (link: https://www.biorxiv.org/content/10.1101/2023.01.25.525562v2)
de la Fuente AG, Dittmer M, Heesbeen E, de la Vega Gallardo N, White J, Young A, Mayne K, Falconer J, McMurran CE, Innayatullah M, Ingram R, Tiwari V, Penalva R, Dombrowski Y, Fitzgerald DC. (2023). bioRxiv.
Brain regulatory T cells (link: https://pubmed.ncbi.nlm.nih.gov/38040953/)
Liston A, Pasciuto E, Fitzgerald DC, Yshii L. (2023). Nat Rev Immunol.
Central and peripheral myeloid-derived suppressor cell-like cells are closely related to the clinical severity of multiple sclerosis (link: https://pubmed.ncbi.nlm.nih.gov/37243699/)
Ortega MC, Lebrón-Galán R, Machín-Díaz I, Naughton M, Pérez-Molina I, García-Arocha J, Garcia-Dominguez JM, Goicoechea-Briceño H, Vila-Del Sol V, Quintanero-Casero V, García-Montero R, Galán V, Calahorra L, Camacho-Toledano C, Martínez-Ginés ML, Fitzgerald DC, Clemente D. (2023). Acta Neuropathol.
Reduced Cone Density Is Associated with Multiple Sclerosis (link: https://pubmed.ncbi.nlm.nih.gov/37214765/)
McIlwaine G, Csincsik L, Coey R, Wang L, Fitzgerald D, Moffat J, Dubis AM, McDonnell G, Hughes S, Peto T, Lengyel I. (2023). Ophthalmol Sci.
Complement activation and increased anaphylatoxin receptor expression are associated with cortical grey matter lesions and the compartmentalised inflammatory response of multiple sclerosis (link: https://pubmed.ncbi.nlm.nih.gov/37032838/)
Evans R, Watkins LM, Hawkins K, Santiago G, Demetriou C, Naughton M, Dittmer M, Rees MI, Fitzgerald D, Morgan BP, Neal JW, Howell OW. (2023). Front Cell Neurosci.
2022
A Review of Compartmentalised Inflammation and Tertiary Lymphoid Structures in the Pathophysiology of Multiple Sclerosis (link: https://pubmed.ncbi.nlm.nih.gov/36289863/)
Kee R, Naughton M, McDonnell GV, Howell OW, Fitzgerald DC. (2022) Biomedicines.
Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage (link: https://pubmed.ncbi.nlm.nih.gov/35538884/)
Matute-Blanch C, Brito V, Midaglia L, Villar LM, Garcia-Diaz Barriga G, Guzman de la Fuente A, Borrás E, Fernández-García S, Calvo-Barreiro L, Miguez A, Costa-Frossard L, Pinteac R, Sabidó E, Alberch J, Fitzgerald DC, Montalban X, Comabella M. (2022). Clin Transl Med.
2021
Research priorities for neuroimmunology: identifying the key research questions to be addressed by 2030 (link: https://pubmed.ncbi.nlm.nih.gov/34778569/)
MacKenzie G, Subramaniam S, Caldwell LJ, Fitzgerald D, Harrison NA, Hong S, Irani SR, Khandaker GM, Liston A, Miron VE, Mondelli V, Morgan BP, Pariante C, Shah DK, Taams LS, Teeling JL, Upthegrove R. (2021). Wellcome Open Res.
Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis (link: https://pubmed.ncbi.nlm.nih.gov/33184094/)
Cunniffe N, Vuong KA, Ainslie D, Baker D, Beveridge J, Bickley S, Camilleri P, Craner M, Fitzgerald D, de la Fuente AG, Giovannoni G, Gray E, Hazlehurst L, Kapoor R, Kaur R, Kozlowski D, Lumicisi B, Mahad D, Neumann B, Palmer A, Peruzzotti-Jametti L, Pluchino S, Robertson J, Rothaul A, Shellard L, Smith KJ, Wilkins A, Williams A, Coles A. (2021). J Neurol Neurosurg Psychiatry.
2020
CCN3 is dynamically regulated by treatment and disease state in multiple sclerosis (link: https://pubmed.ncbi.nlm.nih.gov/33222687/)
Naughton M, Moffat J, Eleftheriadis G, de la Vega Gallardo N, Young A, Falconer J, Hawkins K, Pearson B, Perbal B, Hogan A, Moynagh P, Loveless S, Robertson NP, Gran B, Kee R, Hughes S, McDonnell G, Howell O, Fitzgerald DC. (2020). J Neuroinflammation.
Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition (link: https://pubmed.ncbi.nlm.nih.gov/32702313/)
Pasciuto E, Burton OT, Roca CP, Lagou V, Rajan WD, Theys T, Mancuso R, Tito RY, Kouser L, Callaerts-Vegh Z, de la Fuente AG, Prezzemolo T, Mascali LG, Brajic A, Whyte CE, Yshii L, Martinez-Muriana A, Naughton M, Young A, Moudra A, Lemaitre P, Poovathingal S, Raes J, De Strooper B, Fitzgerald DC, Dooley J, Liston A. (2020). Cell.
Dynamic CCN3 expression in the murine CNS does not confer essential roles in myelination or remyelination (link: https://pubmed.ncbi.nlm.nih.gov/32651278/)
de la Vega Gallardo N, Penalva R, Dittmer M, Naughton M, Falconer J, Moffat J, de la Fuente AG, Hombrebueno JR, Lin Z, Perbal B, Ingram RJ, Evergren E, Fitzgerald DC. (2020). Proc Natl Acad Sci USA.
Changes in the Oligodendrocyte Progenitor Cell Proteome with Ageing (link: https://pubmed.ncbi.nlm.nih.gov/32434922/)
de la Fuente AG, Queiroz RML, Ghosh T, McMurran CE, Cubillos JF, Bergles DE, Fitzgerald DC, Jones CA, Lilley KS, Glover CP, Franklin RJM. (2020). Mol Cell Proteomics.
2019
The microbiota regulates murine inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination (link: https://pubmed.ncbi.nlm.nih.gov/31740610/)
McMurran CE, Guzman de la Fuente A, Penalva R, Ben Menachem-Zidon O, Dombrowski Y, Falconer J, Gonzalez GA, Zhao C, Krause FN, Young AMH, Griffin JL, Jones CA, Hollins C, Heimesaat MM, Fitzgerald DC, Franklin RJM. (2019). Proc Natl Acad Sci USA.
Protective and Regenerative Roles of T Cells in Central Nervous System Disorders (link: https://pubmed.ncbi.nlm.nih.gov/31572381/)
Evans FL, Dittmer M, de la Fuente AG, Fitzgerald DC. (2019). Front Immunol.
Regenerating CNS myelin: Emerging roles of regulatory T cells and CCN proteins (link: https://pubmed.ncbi.nlm.nih.gov/30513363/)
de la Vega Gallardo N, Dittmer M, Dombrowski Y, Fitzgerald DC. (2019). Neurochem Int.
2018
Meningeal inflammation and cortical demyelination in acute multiple sclerosis (link: https://pubmed.ncbi.nlm.nih.gov/30362156/)
Bevan RJ, Evans R, Griffiths L, Watkins LM, Rees MI, Magliozzi R, Allen I, McDonnell G, Kee R, Naughton M, Fitzgerald DC, Reynolds R, Neal JW, Howell OW. (2018). Ann Neurol.
Characterization of a murine mixed neuron-glia model and cellular responses to regulatory T cell-derived factors (link: https://pubmed.ncbi.nlm.nih.gov/29720228/)
Dittmer M, Young A, O’Hagan T, Eleftheriadis G, Bankhead P, Dombrowski Y, Medina RJ, Fitzgerald DC. (2018). Mol Brain.
2017
IL-17 Receptor A Maintains and Protects the Skin Barrier To Prevent Allergic Skin Inflammation (link: https://pubmed.ncbi.nlm.nih.gov/28615416/)
Floudas A, Saunders SP, Moran T, Schwartz C, Hams E, Fitzgerald DC, Johnston JA, Ogg GS, McKenzie AN, Walsh PT, Fallon PG. (2017). J Immunol.
Regulatory T cells promote myelin regeneration in the central nervous system (link: https://pubmed.ncbi.nlm.nih.gov/28288125/)
Dombrowski Y, O’Hagan T, Dittmer M, Penalva R, Mayoral SR, Bankhead P, Fleville S, Eleftheriadis G, Zhao C, Naughton M, Hassan R, Moffat J, Falconer J, Boyd A, Hamilton P, Allen IV, Kissenpfennig A, Moynagh PN, Evergren E, Perbal B, Williams AC, Ingram RJ, Chan JR, Franklin RJM, Fitzgerald DC. (2017). Nat Neurosci.
2016
In vitro and ex vivo models of multiple sclerosis (link: https://pubmed.ncbi.nlm.nih.gov/27265771/)
Madill M, Fitzgerald D, O’Connell KE, Dev KK, Shen S, FitzGerald U. (2016). Drug Discov Today.
CNS Remyelination and the Innate Immune System (link: https://pubmed.ncbi.nlm.nih.gov/27200350/)
McMurran CE, Jones CA, Fitzgerald DC, Franklin RJ. (2016). Front Cell Dev Biol.
Innate Lymphoid Cells Are the Predominant Source of IL-17A during the Early Pathogenesis of Acute Respiratory Distress Syndrome (link: https://pubmed.ncbi.nlm.nih.gov/26488187/)
Muir R, Osbourn M, Dubois AV, Doran E, Small DM, Monahan A, O’Kane CM, McAllister K, Fitzgerald DC, Kissenpfennig A, McAuley DF, Ingram RJ. (2016). Am J Respir Crit Care Med.
2015
Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination (link: https://pubmed.ncbi.nlm.nih.gov/26463675/)
Natrajan MS, de la Fuente AG, Crawford AH, Linehan E, Nuñez V, Johnson KR, Wu T, Fitzgerald DC, Ricote M, Bielekova B, Franklin RJ. (2015). Brain.
Targeting Siglecs with a sialic acid-decorated nanoparticle abrogates inflammation (link: https://pubmed.ncbi.nlm.nih.gov/26333936/)
Spence S, Greene MK, Fay F, Hams E, Saunders SP, Hamid U, Fitzgerald M, Beck J, Bains BK, Smyth P, Themistou E, Small DM, Schmid D, O’Kane CM, Fitzgerald DC, Abdelghany SM, Johnston JA, Fallon PG, Burrows JF, McAuley DF, Kissenpfennig A, Scott CJ. (2015). Sci Transl Med.
2014
Interferon regulatory factor (IRF) 3 is critical for the development of experimental autoimmune encephalomyelitis (link: https://pubmed.ncbi.nlm.nih.gov/25069698/)
Fitzgerald DC, O’Brien K, Young A, Fonseca-Kelly Z, Rostami A, Gran B. (2014). J Neuroinflammation.
Aging impairs peritoneal but not bone marrow-derived macrophage phagocytosis (link: https://pubmed.ncbi.nlm.nih.gov/24813244/)
Linehan E, Dombrowski Y, Snoddy R, Fallon PG, Kissenpfennig A, Fitzgerald DC. (2014). Aging Cell.
2013
Independent and interdependent immunoregulatory effects of IL-27, IFN-β, and IL-10 in the suppression of human Th17 cells and murine experimental autoimmune encephalomyelitis (link: https://pubmed.ncbi.nlm.nih.gov/23455508/)
Fitzgerald DC, Fonseca-Kelly Z, Cullimore ML, Safabakhsh P, Saris CJ, Zhang GX, Rostami A. (2013). J Immunol.
Regulation of Foxp3+ inducible regulatory T cell stability by SOCS2 (link: https://pubmed.ncbi.nlm.nih.gov/23455506/)
Knosp CA, Schiering C, Spence S, Carroll HP, Nel HJ, Osbourn M, Jackson R, Lyubomska O, Malissen B, Ingram R, Fitzgerald DC, Powrie F, Fallon PG, Johnston JA, Kissenpfennig A. (2013). J Immunol.
2012
Cutting edge: suppression of GM-CSF expression in murine and human T cells by IL-27 (link: https://pubmed.ncbi.nlm.nih.gov/22837488/)
Young A, Linehan E, Hams E, O’Hara Hall AC, McClurg A, Johnston JA, Hunter CA, Fallon PG, Fitzgerald DC. (2012). J Immunol.
Intravenous tolerance effectively overcomes enhanced pro-inflammatory responses and experimental autoimmune encephalomyelitis severity in the absence of IL-12 receptor signalling (link: https://pubmed.ncbi.nlm.nih.gov/22522341/)
Fitzgerald DC, Zhang GX, Yu S, Cullimore ML, Zhao Z, Rostami A. (2012). J Neuroimmunol.
A robust co-localisation measurement utilising z-stack image intensity similarities for biological studies (link: https://pubmed.ncbi.nlm.nih.gov/22363456/)
Wang Y, Ledgerwood C, Grills C, Fitzgerald DC, Hamilton PW. (2012). PLoS One.
Para-inflammation-mediated retinal recruitment of bone marrow-derived myeloid cells following whole-body irradiation is CCL2 dependent (link: https://pubmed.ncbi.nlm.nih.gov/22362506/)
Chen M, Zhao J, Luo C, Pandi SP, Penalva RG, Fitzgerald DC, Xu H. (2012). Glia.
2011
Altered Toll-like receptor 2-mediated endotoxin tolerance is related to diminished interferon beta production (link: https://pubmed.ncbi.nlm.nih.gov/21705332/)
Zaric SS, Coulter WA, Shelburne CE, Fulton CR, Zaric MS, Scott A, Lappin MJ, Fitzgerald DC, Irwin CR, Taggart CC. (2011). J Biol Chem.
SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses (link: https://pubmed.ncbi.nlm.nih.gov/21646394/)
Knosp CA, Carroll HP, Elliott J, Saunders SP, Nel HJ, Amu S, Pratt JC, Spence S, Doran E, Cooke N, Jackson R, Swift J, Fitzgerald DC, Heaney LG, Fallon PG, Kissenpfennig A, Johnston JA. (2011). J Exp Med.
2010
Oral resveratrol reduces neuronal damage in a model of multiple sclerosis (link: https://pubmed.ncbi.nlm.nih.gov/21107122/)
Shindler KS, Ventura E, Dutt M, Elliott P, Fitzgerald DC, Rostami A. (2010). J Neuroophthalmol.
Induction of distinct neurologic disease manifestations during relapsing fever requires T lymphocytes (link: https://pubmed.ncbi.nlm.nih.gov/20382883/)
Liu H, Fitzgerald D, Gran B, Leong JM, Alugupalli KR. (2010). J Immunol.
The TLR7 agonist, imiquimod, increases IFN-beta production and reduces the severity of experimental autoimmune encephalomyelitis (link: https://pubmed.ncbi.nlm.nih.gov/20138374/)
O’Brien K, Fitzgerald D, Rostami A, Gran B. (2010). J Neuroimmunol.
2009
Adult neural stem cells expressing IL-10 confer potent immunomodulation and remyelination in experimental autoimmune encephalitis (link: https://pubmed.ncbi.nlm.nih.gov/19884657/)
Yang J, Jiang Z, Fitzgerald DC, Ma C, Yu S, Li H, Zhao Z, Li Y, Ciric B, Curtis M, Rostami A, Zhang GX. (2009). J Clin Invest.
Differential effect of IL-27 on developing versus committed Th17 cells (link: https://pubmed.ncbi.nlm.nih.gov/19786534/)
El-behi M, Ciric B, Yu S, Zhang GX, Fitzgerald DC, Rostami A. (2009). J Immunol.
Functional interleukin-17 receptor A is expressed in central nervous system glia and upregulated in experimental autoimmune encephalomyelitis (link: https://pubmed.ncbi.nlm.nih.gov/19400960/)
Das Sarma J, Ciric B, Marek R, Sadhukhan S, Caruso ML, Shafagh J, Fitzgerald DC, Shindler KS, Rostami A. (2009). J Neuroinflammation.
Therapeutic potential of IL-27 in multiple sclerosis? (link: https://pubmed.ncbi.nlm.nih.gov/19236245/)
Fitzgerald DC, Rostami A. (2009). Expert Opin Biol Ther.
MOG(35-55) i.v suppresses experimental autoimmune encephalomyelitis partially through modulation of Th17 and JAK/STAT pathways (link: https://pubmed.ncbi.nlm.nih.gov/19224632/)
Jiang Z, Li H, Fitzgerald DC, Zhang GX, Rostami A. (2009). Eur J Immunol.
Intravenous tolerance modulates macrophage classical activation and antigen presentation in experimental autoimmune encephalomyelitis (link: https://pubmed.ncbi.nlm.nih.gov/19187972/)
Li H, Ciric B, Yang J, Xu H, Fitzgerald DC, Elbehi M, Fonseca-Kelly Z, Yu S, Zhang GX, Rostami A. (2009). J Neuroimmunol.
2008
IL-12R beta 2 promotes the development of CD4+CD25+ regulatory T cells (link: https://pubmed.ncbi.nlm.nih.gov/18768841/)
Zhao Z, Yu S, Fitzgerald DC, Elbehi M, Ciric B, Rostami AM, Zhang GX. (2008). J Immunol.
CD11c+CD11b+ dendritic cells play an important role in intravenous tolerance and the suppression of experimental autoimmune encephalomyelitis (link: https://pubmed.ncbi.nlm.nih.gov/18684939/)
Li H, Zhang GX, Chen Y, Xu H, Fitzgerald DC, Zhao Z, Rostami A. (2008). J Immunol.
Role of the innate immune system in autoimmune inflammatory demyelination (link: https://pubmed.ncbi.nlm.nih.gov/18473806/)
O’Brien K, Fitzgerald DC, Naiken K, Alugupalli KR, Rostami AM, Gran B. (2008). Curr Med Chem.
2007
Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells (link: https://pubmed.ncbi.nlm.nih.gov/17994023/)
Fitzgerald DC, Zhang GX, El-Behi M, Fonseca-Kelly Z, Li H, Yu S, Saris CJ, Gran B, Ciric B, Rostami A. (2007). Nat Immunol.
Suppressive effect of IL-27 on encephalitogenic Th17 cells and the effector phase of experimental autoimmune encephalomyelitis (link: https://pubmed.ncbi.nlm.nih.gov/17709543/)
Fitzgerald DC, Ciric B, Touil T, Harle H, Grammatikopolou J, Das Sarma J, Gran B, Zhang GX, Rostami A. (2007). J Immunol.
2006
Cutting Edge: TLR3 stimulation suppresses experimental autoimmune encephalomyelitis by inducing endogenous IFN-beta (link: https://pubmed.ncbi.nlm.nih.gov/17114417/)
Touil T, Fitzgerald D, Zhang GX, Rostami A, Gran B. (2006). J Immunol.