A06

A06: Summary

cAMP is an ubiquitous second messenger that is essential for regulatory T cell (Treg)-mediated immunosuppression. When transferred between Treg and effector T cells (Teff), it can suppress various immune responses. Using a highly sensitive fluorescent biosensor expressed in transgenic mice to monitor cAMP in T cells in combination with tissue preparations and multiple sclerosis disease models, we will study the mechanistic basis of cAMP signaling in Treg and Teff cells by live cell imaging of cAMP generation, degradation and transfer between both T cell populations ex vivo and in vivo.

Prof. Dr. Viacheslav O. Nikolaev

Selected publications

 

  1. Jungen C, Scherschel K, Eickholt C, Kuklik P, Klatt N, Bork N, Salzbrunn T, Alken F, Angendohr S, Klene C, Mester J, Klöcker N, Veldkamp MW, Schumacher U, Willems S, Nikolaev VO*, Meyer C* (2017) Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias. Nature Commun 8:14155.
  2. Sprenger JU, Perera RK, Steinbrecher JH, Lehnart SE, Maier LS, Hasenfuss G, Nikolaev VO (2015) In vivo model with targeted cAMP biosensor reveals changes in receptor-microdomain communication in cardiac disease. Nature Commun 6:6965.
  3. Perera RK, Sprenger JU, Steinbrecher JH, Hübscher D, Lehnart SE, Abesser M, Schuh K, ElArmouche A, Nikolaev VO (2015) Microdomain switch of cGMP-regulated phosphodiesterases leads to ANP-Induced augmentation of beta-adrenoceptor-stimulated contractility in early cardiac hypertrophy. Circ Res 116:1304-1311.
  4. Börner S, Schwede F, Schlipp A, Berisha F, Calebiro D, Lohse MJ, Nikolaev VO (2011) FRET measurements of intracellular cAMP concentrations and cAMP analog permeability in intact cells. Nature Protoc 6:427-438.
  5. Nikolaev VO, Moshkov A, Lyon AR, Miragoli M, Novak P, Paur H, Lohse MJ, Korchev YE, Harding SE, Gorelik J. (2010) Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation. Science 327:1653-1657.
  6. Calebiro D*, Nikolaev VO*, Gagliani MC, de Filippis T, Dees C, Tacchetti C, Persani L, Lohse MJ (2009) Persistent cAMP-signals triggered by internalized G-protein-coupled receptors. PLoS Biol 7:e1000172.
  7. Vilardaga JP, Nikolaev VO, Lorenz K, Ferrandon S, Zhuang Z, Lohse MJ (2008) Conformational cross-talk between α2A-adrenergic and μ-opioid receptors controls cell signaling. Nature Chem Biol 4:126-131.
  8. Nikolaev VO, Boivin V, Stork S, Angermann CE, Ertl G, Lohse MJ, Jahns R (2007) A novel fluorescence method for the rapid detection of functional β1-adrenergic receptor autoantibodies in heart failure. J Am Coll Cardiol 50:423-431.
  9. Nikolaev VO, Bünemann M, Schmitteckert E, Lohse MJ, Engelhardt S (2006) Cyclic AMP imaging in adult cardiac myocytes reveals far-reaching beta1-adrenergic but locally confined beta2-adrenergic receptor-mediated signaling. Circ Res 99:1084-1091.
  10. Nikolaev VO, Gambaryan S, Lohse MJ (2006) Fluorescent sensors for rapid monitoring of intracellular cGMP. Nature Methods 3:23-25. * shared first/senior authorship

 

 

 

 

Prof. Dr. Manuel Alexander Friese

Selected publications

 

  1. Engler JB, Kursawe N, Solano ME, Patas K, Wehrmann S, Heckmann N, Lühder F, Reichardt HM, Arck PC, Gold SM, Friese MA (2017) Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy. Proc Natl Acad Sci USA 114:E181-E190.
  2. Schattling B, Fazeli W, Engeland B, Liu Y, Lerche H, Isbrandt D, Friese MA (2016) Activity of Na(V)1.2 promotes neurodegeneration in an animal model of multiple sclerosis. JCI Insight 1:e89810.
  3. Ufer F, Vargas P, Engler JB, Tintelnot J, Schattling B, Winkler H, Bauer S, Kursawe N, Willing A, Keminer O, Ohana O, Salinas-Riester G, Pless O, Kuhl D, Friese MA (2016) Arc/Arg3.1 governs inflammatory dendritic cell migration from the skin and thereby controls T cell activation. Sci Immunol 1:eaaf8665.
  4. Piédavent-Salomon M*, Willing A*, Engler JB, Steinbach K, Bauer S, Eggert B, Ufer F, Kursawe N, Wehrmann S, Jäger J, Reinhardt S, Friese MA (2015) Multiple sclerosis associated genetic variants of CD226 impair regulatory T cell function. Brain.138:3263-3264. *both authors contributed equally
  5. Willing A, Leach OA, Ufer F, Attfield KE, Steinbach K, Kursawe N, Piedavent M, Friese MA (2014) CD8+ MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL-18 serum levels in multiple sclerosis. Eur J Immunol 44:3119-3128.
  6. Steinbach K, Piedavent M, Bauer S, Neumann JT, Friese MA (2013) Neutrophils amplify autoimmune central nervous system infiltrates by maturing local APCs. J Immunol 191:4531-4539.
  7. Schattling B, Steinbach K, Thies E, Kruse M, Menigoz A, Ufer F, Flockerzi V, Brück W, Pongs O, Vennekens R, Kneussel M, Freichel M, Merkler D, Friese MA (2012) TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med 1805-1811.
  8. Friese MA, Jakobsen KB, Friis L, Etzensperger R, Craner MJ, McMahon RM, Jensen LT, Huygelen V, Jones EY, Bell JI, Fugger L (2008) Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis. Nat Med 11:1227-1235.
  9. Tzartos JS*, Friese MA*, Craner MJ, Palace J, Newcombe J, Esiri MM, Fugger L (2008) Interleukin17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 172:146-155. *both authors contributed equally
  10. Friese MA, Craner MJ, Etzensperger R, Vergo S, Wemmie JA, Welsh MJ, Vincent A, Fugger L (2007) Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system. Nat Med 12:1483-1489.

Our Team

Prof. Dr. Viacheslav Nikolaev

Dept. of Experimental Cardiovascular Research

University Medical Centre Hamburg-Eppendorf (UKE)

Prof. Dr. Manuel Friese

Institute of Neuroimmunology and Multiple Sclerosis (INIMS)

Center for Molecular Neurobiology Hamburg (ZMNH)

M.Sc. Roberta Kurelic

Dept. of Experimental Cardiovascular Research

University Medical Centre Hamburg-Eppendorf (UKE)

M.Sc. Marlena Scharenberg

Institute of Neuroimmunology and Multiple Sclerosis (INIMS)

Center for Molecular Neurobiology Hamburg (ZMNH)

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