A13

A13 Project movie

A13

Inflammatory processes in the CNS have been studied in project A13. Stroke, a sterile inflammatory process, resulted in rapid release of ATP, as shown by ATP-sensor expressing mice, leading to P2X7 activation in microglial cells. Stroke damage was increased in mice overexpressing P2X7, and intracerebral administration of nanobodies blocking P2X7 resulted in smaller stroke sizes in the treated animals, underscoring the role  of P2X7 in the amplification of inflammation after stroke. Studying the role of ATP degrading ectoenzymes in brain endothelial cells (EC) and microglia revealed high expression of CD73 in the human system, while murine EC and microglia did not express CD73. Together with project A14, project A13showed that a human brain endothelial cell line produced EVs that suppressed T cell function in a CD73-dependent manner. Further, project A13 found that stroke induced changes in the cargo and cellular origin of brain-derived EVs account for the lack of effect of Nt5e deletion on stroke size. Moreoverr, together with project A14, project A13 showed that for humans, CD73 expressed on cerebral EC can have a decisive impact on the activation status of human effector T cells.  Further, this impact can even come in forms of CD73-containing EVs.

Prof. Dr. Tim Magnus

Selected publications (*equal contribution)

 

  1. Brenna S, Altmeppen HC, Mohammadi B, Rissiek B, Schlink F, Ludewig P, Krisp C, Schlüter H, Failla AV, Schneider C, Glatzel M, Puig B, Magnus T (2020) Characterization of brain-derived extracellular vesicles reveals changes in cellular origin after stroke and enrichment of the prion protein with a potential role in cellular uptake. J Extracell Vesicles 9(1):1809065.
  2. Gelderblom M, Gallizioli M, Ludewig P, Thom V, Arunachalam P, Rissiek B, Bernreuther C, Glatzel M, Korn T, Arumugam TV, Sedlacik J, Gerloff C, Tolosa E, Planas AM, Magnus T (2018) IL-23 (Interleukin-23)-Producing Conventional Dendritic Cells Control the Detrimental IL-17 (Interleukin-17) Response in Stroke. Stroke 49(1):155-164.
  3. Ludewig P, Gdaniec N, Sedlacik J, Forkert ND, Szwargulski P, Graeser M, Adam G, Kaul MG, Krishnan KM, Ferguson RM, Khandhar AP, Walczak P, Fiehler J, Thomalla G, Gerloff C, Knopp T, Magnus T (2017) Magnetic Particle Imaging for Real-time Perfusion Imaging in Acute Stroke. ACS Nano 11:10480-10488.
  4. Gelderblom M, Melzer N, Schattling B, Göb E, Hicking G, Arunachalam P, Bittner S, Ufer F, Herrmann AM, Bernreuther C, Glatzel M, Gerloff C, Kleinschnitz C, Meuth SG, Friese MA, Magnus T (2014) Transient receptor potential melastatin subfamily member 2 cation channel regulates detrimental immune cell invasion in ischemic stroke. Stroke 45:3395-3402
  5. Ludewig P, Sedlacik J, Gelderblom M, Bernreuther C, Korkusuz Y, Wagener C, Gerloff C, Fiehler J, Magnus T*, Horst AK*.  (2013) Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Inhibits MMP-9-Mediated Blood-Brain-Barrier Breakdown in a Mouse Model for Ischemic Stroke. Circ Res 113:1013-1022.
  6. Gelderblom M, Daehn T, Schattling B, Ludewig P, Bernreuther C, Arunachalam P, Matschke J, Glatzel M, Gerloff C, Friese MA, Magnus T (2013) Plasma levels of neuron specific enolase quantify the extent of neuronal injury in murine models of ischemic stroke and multiple sclerosis. Neurobiol Dis 59:177-182
  7. Gelderblom M, Weymar A, Bernreuther C, Velden J, Arunachalam P, Steinbach K, Orthey E, Arumugam TV, Leypoldt F, Simova O, Thom V, Friese MA, Prinz I, Hölscher C, Glatzel M, Korn T, Gerloff C, Tolosa E, Magnus T (2012) Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke. Blood 120:3793-3802
  8. Gelderblom M, Leypoldt F, Steinbach K, Behrens D, Choe CU, Siler DA, Arumugam TV, Orthey E, Gerloff C, Tolosa E, Magnus T (2009) Temporal and spatial dynamics of cerebral immune cell accumulation in stroke. Stroke 40(5):1849-57.
  9. Arumugam TV, Chan SL, Jo DG, Yilmaz G, Tang SC, Cheng A, Gleichmann M, Okun E, Dixit VD, Chigurupati S, Mughal MR, Ouyang X, Miele L, Magnus T, Poosala S, Granger DN, Mattson MP (2006) Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke. Nat Med 12(6):621-3.
  10. Mattson MP, Magnus T (2006) Ageing and neuronal vulnerability. Nat Rev Neurosci 7:278-294

Prof. Dr. Eva Tolosa

Selected publications (*equal contribution)

 

  1. Schneider E, Winzer R, Rissiek A, Ricklefs I, Meyer-Schwesinger C, Ricklefs FL, Bauche A, Behrends J, Reimer R, Brenna S, Wasielewski H, Lauten M, Rissiek B, Puig B, Cortesi F, Magnus T, Fliegert R, Müller CE, Gagliani N, Tolosa E (2021) CD73-mediated adenosine production by CD8 T cell-derived extracellular vesicles constitutes an intrinsic mechanism of immune suppression. Nat Commun 125911.
  2. Schneider E, Rissiek A, Winzer R, Puig B, Rissiek B, Haag F, Mittrücker HW, Magnus T, Tolosa E (2019) Generation and Function of Non-cell-bound CD73 in Inflammation. Front Immunol 10:1729
  3. Solano ME, Holmes MC, Mittelstadt PR, Chapman KE*, Tolosa E* (2016) Antenatal endogenous and exogenous glucocorticoids and their impact on immune ontogeny and long-term immunity. Semin Immunopathol 38:739-763.
  4. Rissiek A, Baumann I, Cuapio A, ter Haar N, Kolster M, Dodge-Khatami A, Arck PC, Mittrücker HW, Koch-Nolte F, Haag F, Tolosa E (2015) The expression of CD39 on regulatory T cells is genetically driven and further upregulated at sites of inflammation. J Autoimmunity 58:12-20.
  5. Diepenbruck I, Much CC, Krumbholz A, Kolster M, Thieme R, Thieme D, Solano ME, Arck PC, Tolosa E (2013) Effect of prenatal steroid treatment on the developing immune system. J Mol Med (Berl) 91:1293-1302.
  6. Stoeckle C, Quecke P, Rückrich T, Burster T, Reich M, Weber E, Kalbacher H, Driessen C, Melms A, Tolosa E (2012) Cathepsin S dominates autoantigen processing in human thymic dendritic cells. J Autoimmun. 38:332-343.
  7. Gelderblom M, Weymar A, Bernreuther C, Velden J, Arunachalam P, Steinbach K, Orthey E, Arumugam TV, Leypoldt F, Simova O, Thom V, Friese MA, Prinz I, Hölscher C, Glatzel M, Korn T, Gerloff C, Tolosa E, Magnus T (2012) Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke. Blood 120:3793-3802.
  8. Brucklacher-Waldert V, Stuerner K, Kolster M, Wolthausen J, Tolosa E (2009) Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis. Brain 132:3329-3341.
  9. Brucklacher-Waldert V, Steinbach K, Kolster M, Lioznov M, Hoelscher C, Tolosa E (2009) Phenotypical and functional characterization of human Th17 cells unambiguously identified by surface IL-17A expression. J Immunol 183:5494-5501.
  10. Feger U*, Tolosa E *, Yu-Hwa H*, Biedermann T, Melms A, Wiendl H (2007) HLA-G expression defines a novel regulatory T cell subset present in human peripheral blood and sites of neuroinflammation. Blood 110:568-577 (*shared authorship).

Our Team

Prof. Dr. Tim Magnus

Department of Neurology

University Medical Center Hamburg-Eppendorf (UKE)

Prof. Dr. Eva Tolosa

Insitute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

Dr. Björn Rissiek

Department of Neurology

University Medical Center Hamburg-Eppendorf (UKE)

M. Sc. Enja Schneider

Insitute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

Dr. Anne Rissiek

Insitute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

Laura Glau

Insitute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

Contact

University Medical Center Hamburg-Eppendorf 
Department of Biochemistry and Molecular Cell Biology 
Martinistrasse 52
20246 Hamburg

Scientific Coordinator

Dr. Björn-Philipp Diercks
Fon: +49  (0) 40 7410 54338
E-Mail: b.diercks©uke.de

Administration

Laura Mitsching
Fon: +49  (0) 40 7410 50301
E-Mail: l.mitsching©uke.de