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Research Group “Human T cell differentiation and homeostasis”

Dr. Anne Rensing-Ehl

We use human genetic disorders of T cell immunity as a window to understand T cell differentiation and homeostasis.

Research focus

Differentiation and lifespan of T cells have to be precisely balanced to maintain homeostasis and self-tolerance. We recently described a FAS-controlled (FC) subset of TCRαβ+ T cells that is characterized by a unique molecular signature unambiguously separating it from other known conventional T cell subsets. FC T cells include CD4+, CD8+ and double negative T cells (DNT) and are exceptionally sensitive to FAS-induced apoptosis. They are present in healthy individuals at low frequency, but massively expand in FAS-deficient patients with autoimmune lymphoproliferative syndrome (ALPS). Origin, cell fate induction, differentiation and function of this highly proliferative T cell subset are currently not understood. Further characterization of this unusual T cell population offers an opportunity to identify key steps in the control of differentiation and proliferation of human T cells with potential implications for other benign and malignant lymphoproliferative diseases.

Current projects

  1. Identification of new defects and genetic constellations causing autoimmune lymphoproliferative syndrome (ALPS).
  2. Role of FAS Ligand mutations in the pathogenesis of ALPS.
  3. Delineation of the ontogeny and differentiation of human and murine FAS controlled T cells.
  4. Characterization of the physiological niche, fate inducing signals and function of FAS controlled T cells.

Collaborations

  • Prof. Stephan Ehl, Institute for Immunodeficiency, Medical Center - University of Freiburg
  • Dr. Peter Aichele, Institute for Immunodeficiency, Medical Center - University of Freiburg
  • Prof. Klaus Schwarz, Institut für Klinische Transfusionsmedizin und Immungenetik Ulm (IKT)
  • PD Marta Rizzi, Department of Rheumatology and Clinical Immunology, Freiburg
  • Prof. Tomas Kalina, Faculty of Medicine, Charles University Prague
  • Prof. Herve Luche, CIPHE Department, University Marseille

CV

 
Since 2022 Group leader, Institute for Immunodeficiency, Medical Center - University of Freiburg
2008-2022 Postdoctorate, Institute for Immunodeficiency, Medical Center - University of Freiburg
2005-2008 Postdoctorate, Department of Dermatology, Medical Center - University of Freiburg
1994-1995 Postdoctorate, Clinical Immunology, Universtity of Zurich
1993-1994 Postdoctorate, Institute for Immunology, University of Munich (LMU)
1991-1992 MD Thesis in Rheumatology and Immunology, University of Erlangen (Supervisor: Prof. Gerd Burmester)
1985-1992 Study of Medicine in Aachen, Birmingham, Erlangen and Munich

Publications

  1. Maccari, M. E., S. Fuchs, P. Kury, G. Andrieux, S. Volkl, B. Bengsch, M. R. Lorenz, M. Heeg, J. Rohr, S. Jagle, C. N. Castro, M. Gross, U. Warthorst, C. Konig, I. Fuchs, C. Speckmann, J. Thalhammer, F. G. Kapp, M. G. Seidel, G. Duckers, S. Schonberger, C. Schutz, M. Fuhrer, R. Kobbe, D. Holzinger, C. Klemann, P. Smisek, S. Owens, G. Horneff, R. Kolb, N. Naumann-Bartsch, M. Miano, J. Staniek, M. Rizzi, T. Kalina, P. Schneider, A. Erxleben, R. Backofen, A. Ekici, C. M. Niemeyer, K. Warnatz, B. Grimbacher, H. Eibel, A. Mackensen, A. P. Frei, K. Schwarz, M. Boerries, S. Ehl, and A. Rensing-Ehl. 2021. A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS. J Exp Med 218: pii: 211525. doi: 10.1084/jem.20192191.
  2. Klemann, C., M. Esquivel, A. Magerus-Chatinet, M. R. Lorenz, I. Fuchs, N. Neveux, M. Castelle, J. Rohr, C. B. da Cunha, M. Ebinger, R. Kobbe, B. Kremens, F. Kollert, E. Gambineri, K. Lehmberg, M. G. Seidel, K. Siepermann, T. Voelker, V. Schuster, S. Goldacker, K. Schwarz, C. Speckmann, C. Picard, A. Fischer, F. Rieux-Laucat, S. Ehl, A. Rensing-Ehl#, and B. Neven#. 2017. Evolution of disease activity and biomarkers on and off rapamycin in 28 patients with autoimmune lymphoproliferative syndrome. Haematologica 102: e52-e56. doi: 10.3324/haematol.2016.153411.
  3. Volkl, S.*, A. Rensing-Ehl*, A. Allgauer, E. Schreiner, M. R. Lorenz, J. Rohr, C. Klemann, I. Fuchs, V. Schuster, A. O. von Bueren, N. Naumann-Bartsch, E. Gambineri, K. Siepermann, R. Kobbe, M. Nathrath, P. D. Arkwright, M. Miano, K. D. Stachel, M. Metzler, K. Schwarz, A. N. Kremer, C. Speckmann, S. Ehl, and A. Mackensen. 2016. Hyperactive mTOR pathway promotes lymphoproliferation and abnormal differentiation in autoimmune lymphoproliferative syndrome. Blood 128: 227-238. doi: 10.1182/blood-2015-11-685024.
  4. Fuchs S.*, Rensing-Ehl A*, Pannicke U.*, Lorenz MR, Fisch P, Jeelall Y, Rohr J, Speckmann C, Vraetz T, Farmand S, Schmitt-Graeff A, Krüger M, Strahm B, Henneke P, Enders A, Horikawa K, Goodnow C, Schwarz K, Ehl S. 2015. Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency. Blood. 126: 1658-69. doi: 10.1182/blood-2015-03-631374.
  5. Rensing-Ehl A, Pannicke U, Zimmermann SY, Lorenz MR, Neven B, Fuchs I, Salzer U, Speckmann C, Strauss A, Maaβ E, Collet B, Enders A, Favier R, Alessi MC, Rieux-Laucat F, Zieger B, Schwarz K, Ehl S. 2015. Gray platelet syndrome can mimic autoimmune lymphoproliferative syndrome. Blood. 126: 1967-9. doi: 10.1182/blood-2015-06-654145.
  6. Stepensky P, Rensing-Ehl A, Gather R, Revel-Vilk S, Fischer U, Nabhani S, Beier F, Brümmendorf TH, Fuchs S, Zenke S, Firat E, Pessach VM, Borkhardt A, Rakhmanov M, Keller B, Warnatz K, Eibel H, Niedermann G, Elpeleg O, Ehl S. 2015. Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency. Blood. 125: 753-61. doi: 10.1182/blood-2014-08-593202.
  7. Rensing-Ehl, A., S. Volkl, C. Speckmann, M. R. Lorenz, J. Ritter, A. Janda, M. Abinun, H. Pircher, B. Bengsch, R. Thimme, I. Fuchs, S. Ammann, A. Allgauer, K. Kentouche, A. Cant, S. Hambleton, C. Bettoni da Cunha, S. Huetker, I. Kuhnle, A. Pekrun, M. G. Seidel, M. Hummel, A. Mackensen, K. Schwarz, and S. Ehl. 2014. Abnormally differentiated CD4+ or CD8+ T-cells with phenotypic and genetic features of double negative T-cells in human Fas deficiency. Blood 124: 851-60. doi: 10.1182/blood-2014-03-564286.
  8. Rensing-Ehl A, A. Janda, M. R. Lorenz, B. P. Gladstone, I. Fuchs, M. Abinun, M. Albert, K. Butler, A. Cant, A. M. Cseh, M. Ebinger, S. Goldacker, S. Hambleton, H. Hebart, L. Houet, K. Kentouche, I. Kuhnle, K. Lehmberg, E. Mejstrikova, C. Niemeyer, M. Minkov, O. Neth, G. Duckers, S. Owens, J. Rosler, F. H. Schilling, V. Schuster, M. G. Seidel, P. Smisek, M. Sukova, P. Svec, T. Wiesel, B. Gathmann, K. Schwarz, W. Vach, S. Ehl, and C. Speckmann. 2013. Sequential decisions on FAS sequencing guided by biomarkers in patients with lymphoproliferation and autoimmune cytopenia. 2013. Haematologica 98: 1948-55. doi: 10.3324/haematol.2012.081901.
  9. Pannicke, U., B. Baumann, S. Fuchs, P. Henneke, A. Rensing-Ehl, M. Rizzi, A. Janda, K. Hese, M. Schlesier, K. Holzmann, S. Borte, C. Laux, E. M. Rump, A. Rosenberg, T. Zelinski, H. Schrezenmeier, T. Wirth, S. Ehl, M. L. Schroeder*, and K. Schwarz*. 2013. Deficiency of innate and acquired immunity caused by an IKBKB mutation. N Engl J Med 369: 2504-2514. doi: 10.1056/NEJMoa1309199.
  10. Maul-Pavicic, A., S. C. Chiang, A. Rensing-Ehl, B. Jessen, C. Fauriat, S. M. Wood, S. Sjoqvist, M. Hufnagel, I. Schulze, T. Bass, W. W. Schamel, S. Fuchs, H. Pircher, C. A. McCarl, K. Mikoshiba, K. Schwarz, S. Feske, Y. T. Bryceson, and S. Ehl. 2011. ORAI1-mediated calcium influx is required for human cytotoxic lymphocyte degranulation and target cell lysis. Proc Natl Acad Sci USA 108: 3324-3329. doi: 10.1073/pnas.1013285108.

*contributed equally
#joint senior authors

 

Group members

Group Leader    
Anne Rensing-Ehl anne.rensing-ehl@uniklinik-freiburg.de  0761-27071080

Clinician scientist group leader

   
Mariaelena Maccari maria.elena-maccari@unikinik-freiburg.de 0761-27043090

PhDs

 

 
Christoph König christoph.koenig@uniklinik-freiburg.de 0761-27071080
Sarah Berger sarah.berger@uniklinik-freiburg.de 0761-27071080