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Molecular and Cellular Immunology/Immune Regulation - Karsten Kretschmer

CD4+Foxp3+ regulatory T (Treg) cells play an essential role in maintaining immune homeostasis in mice and men. A particularly striking example of Foxp3+ Treg cell function that restrains destructive tissue-specific autoimmunity is the observation that acute Treg cell ablation in the NOD mouse model of human type 1 diabetes unleashes overt autoimmune diabetes within days (Petzold et al., 2013). Conversely, Treg cells represent exciting gain-of-function targets in clinical settings of unwanted immune responses, such as autoimmunity. In this context, our research interests focus on molecular and cellular pathways that govern the generation, lifestyle and function of Foxp3+ Treg cells.

Previous and current research

CD4+CD25+ regulatory T cells (Treg) expressing the forkhead family transcription factor Foxp3 play an essential role in establishing dominant self-tolerance, controlling inflammatory responses and maintaining immune homeostasis in mice and men. In recent years, Treg have attracted considerable attention as promising gain-of-function targets in clinical settings of unwanted immune responses, such as organ-specific autoimmunity and immune rejection of transplanted hematopoietic stem cells. In this context, our research interests focus on molecular and cellular pathways of Foxp3+ Treg generation and suppressor function. more

Future projects and goals

  • Molecular and cellular pathways that govern the generation and function of Treg
  • Molecular networks in immunity, tolerance and autoimmunity
  • Treg in homeostatic hematopoiesis and hematopoietic stem cell transplantation
  • Antigen-specific Treg as gain-of-function targets in autoimmune diseases

Selected publications

Recent Publications

 Freudenberg, K. ; Lindner, N. ; Dohnke, S. ; Garbe, A.I. ; Schallenberg, S.* ; Kretschmer, K.* Critical role of TGF-β and Il-2 receptor signaling in Foxp3 induction by an inhibitor of DNA methylation. Front. Immunol. 9:125. (2018)    *Equally contributing last author

 

 Dohnke, S. ; Schreiber, M. ; Schallenberg, S. ; Simonetti, M. ; Fischer, L. ; Garbe, A.I. ; Chatzigeorgiou, A. ; Kretschmer, K. Approaches to discriminate naturally induced Foxp3+ Treg cells of intra- and extrathymic origin: Helios, Neuropilin-1, and Foxp3RFP/GFP. J. Clin. Cell. Immunol. (in press)

 

Tabansky, I.* ; Keskin, D.B.* ; Watts, D.* ; Sands, W. ; Petzold, C. ; Yunis, E.J. ; Cao, Y. ; Mooney, D. ; Kretschmer, K.; Stern, J.N.H.DEC-205DCIR2+ dendritic cell targeting promotes immunological tolerance in proteolipid protein-induced experimental autoimmune encephalomyelitis. Molecular Medicine. (in press)Corresponding and *equally contributing first author

 

 Schallenberg, S. ; Kretschmer, K. New insight into type 1 diabetes development: resolving early diabetogenic CD4+ T cell responses that precede seroconversion. Editorial. Ann. Transl. Med. (2018)                                                   

View this article at: http://atm.amegroups.com/article/view/17966

 

Fuchs, A. ; Gliwiński, M. ; Grageda, N. ; Spiering, R. ; Abbas, A.K. ; Appel, S. ; Berglund, D. ; Blazar, B. ; Bluestone, J. ; …Kretschmer, K. ; …Trzonkowski, P. Minimum information about T regulatory cells (MITREG): a step towards reproducibility and standardization. Front Immunol. 8:1844. (2017)

  

Selected Publications

 Wyss, L. ; Stadinski, B.D. ; King, C.G. ;  Schallenberg, S. ; McCarthy, N.I. ; Lee, J.Y. ; Kretschmer, K. ; Terracciano, L.M. ; Anderson, G. ; Surh, C.D. ; Huseby, E.S. ; Palmer, E. Affinity for self-antigen selects regulatory T cells with distinct functional properties. Nat. Immunol. 17(9):1093-101. (2016)

 

Spiering, R ; Margry, B. ; Keijzer, C. ; Petzold, C. ; Hoek, A. ; Wagenaar, J. ; Arkesteijn, G. ; van der Zee, R. ; van Eden, W. ; Kretschmer, K. ; Broere, F. DEC-205-targeted tolerogenic vaccination promotes immune tolerance in experimental autoimmune arthritis. 2015. J. Immunol. 15;194(10):4804-13. (2015)

 

Warth, S.C. ; Hoefig, K.P. ; Hiekel, A. ; Schallenberg, S. ; Jovanovic, K. ; Klein, L. ; Kretschmer, K. ; Ansel, K.M. ; Heissmeyer, V. Induced miR-99a expression represses Mtor cooperatively with miR-150 to promote regulatory T cell differentiation. EMBO J. 5;34(9):1195-213 (2015)

 

Chmelova, H. ; Cohrs, C.M. ; Chouinard, J.A. ; Petzold, C. ; Kuhn, M. ; Chen, C. ; Roeder, I. ; Kretschmer, K. ; Speier, S. Distinct roles of beta cell mass and function during type 1 diabetes onset and remission. Diabetes. pii: db141055. (2015)

 

Vahl, J.C. ; Drees, C. ; Heger, K. ; Heink, S. ; Fischer, J.C. ; Nedjic, J. ; Ohkura, N. ; Morikawa, H. ; Poeck, H. ; Schallenberg, S. ; Rieß, D. ; Hein, M.Y. ; Buch, T. ; Polic B. ; Schönle, A. ; Zeiser, R. ; Schmitt-Gräff, A. ; Kretschmer, K. ; Klein, L. ; Korn, T. ; Sakaguchi, S. ; Schmidt-Supprian, M. Continuous T Cell Receptor Signals Maintain a Functional Regulatory T Cell Pool. Immunity. 41(5):722-736. (2014)

 

Mayer, C.T. ; Lahl, K. ; Dittmer, U. ; Fyhrquist, N. ; Huehn, J. ; Kopf, M. ; Kretschmer, K. ; Rouse, B. ; Sparwasser, T. Advantages of Foxp3+ regulatory T cell depletion using DEREG mice. Immun Inflamm Dis. 2(3): 162-165. (2014)

 

Petzold, C. ; Steinbronn, N. ; Gereke, M. ; Strasser, R. ; Sparwasser, T. ; Bruder, D. ; Geffers, R. ; Schallenberg, S. ; Kretschmer, K. Fluorochrome reporter-based definition of Foxp3+ regulatory T cell subphenotypes of distinct developmental origin. Eur. J. Immunol. 44(12):3632-45. (2014)

 

Xiao, S. ; Yosef, N. ; Yang, J. ; Wang, Y. ; Zhou, L. ; Zhu, C. ; Wu, C. ; Baloglu, E. ; Schmidt, D. ; Ramesh, R. ; Lobera, M. ; Sundrud, M.S. ; Tsai, P.Y. ; Xiang, Z. ; Wang, J. ; Xu, Y. ; Lin, X. ; Kretschmer, K. ; Rahl, P.B. ; Young, R.A. ; Zhong, Z. ; Hafler, D.A. ; Regev, A. ; Ghosh, S. ; Marson, A. ; Kuchroo, V.K. Small-Molecule ROR gamma t Antagonists Inhibit T Helper 17 Cell Transcriptional Network by Divergent Mechanisms. Immunity. 40(4):477-89. (2014)

 

Toker, A. ; Engelbert, D. ; Garg, G. ; Polansky, J.K. ; Floess, S. ; Miyao, T. ; Baron, U. ; Düber, S. ; Geffers, R. ; Giehr, P. ; Schallenberg, S ; Kretschmer, K. ; Olek, S. ; Walter, J. ; Weiss, S. ; Hori, S. ; Hamann, A. ; Huehn, J. Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus. J Immunol. 1;190(7):3180. (2013)

 

Schallenberg, S. ; Petzold, S. ; Riewaldt, J. ; Kretschmer, K. Regulatory T Cell-Based Immunotherapy: Prospects of Antigen-Specific Tolerance Induction. In: Medical Advancements in Aging and Regenerative Technologies: Clinical Tools and Applications, ed. A. Daskalaki. IGI Global, pp. 112-136. (2013)

 

Petzold, C. ; Riewaldt, J. ; Watts, D. ; Sparwasser, T. ; Schallenberg, S. ; Kretschmer, K. Foxp3+ Regulatory T Cells in Mouse Models of Type 1 Diabetes. J Diabetes Res. 940710. doi: 10.1155/2013/940710. (2013)

 

Heninger, A.K. ; Theil, A. ; Wilhelm, C. ; Petzold, C. ; Huebel, N. ; Kretschmer, K. ; Bonifacio, E. ; Monti, P. IL-7 abrogates suppressive activity of human CD4+CD25+FOXP3+ regulatory T cells and allows expansion of alloreactive and autoreactive T cells. J Immunol. 15;189(12):5649. (2012)

 

Riewaldt, J. ; Düber, S. ; Boernert, M. ; Krey, M. ; Dembinski, M. ; Weiss, S. ; Garbe, A.I. ; Kretschmer, K. Severe developmental B lymphopoietic defects in Foxp3-deficient mice are refractory to adoptive regulatory T cell therapy. Front Immunol. 3:141. (2012)

 

Schallenberg, S. ; Petzold, C. ; Tsai, P.Y. ; Sparwasser, T. ; Kretschmer, K. Vagaries of fluorochrome reporter gene expression in Foxp3+ regulatory T cells. PLoS One. 7(8):e41971. (2012)

 

Petzold, C. ; Schallenberg, S. ; Stern, J.N.H. ; Kretschmer, K. Targeted antigen delivery to DEC-205+ dendritic cells for tolerogenic vaccination. Rev Diabet Stud. 2012; 9(4):305. IF: 2.5; Citations: n/a / 6

 

Stern, J.N.H.*; Keskin, D.B.* ; Kato, Z. ; Waldner, H. ; Schallenberg, S. ; Anderson, A. ; von Boehmer, H. ; Kretschmer, K.*, Strominger JL. Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells. Proc Natl Acad Sci U S A. 107(40):17280. (2010)Corresponding and *equally contributing first author

 

Schallenberg, S. ; Tsai, P.Y. ; Riewaldt, J. ; Kretschmer, K. Identification of an immediate Foxp3 precursor population to Foxp3+ regulatory T cells in peripheral lymphoid organs of non-manipulated mice. J Exp Med. 207(7):1393. (2010)

 

Petzold, C. ; Riewaldt, J. ; Koenig, T. ; Schallenberg, S. ; Kretschmer K. Dendritic cell targeted pancreatic b cell antigen leads to conversion of self-reactive CD4+ T cells into regulatory T cells and immunotolerance in NOD mice. Rev Diabet Stud. 2010. 7(1):45. (2010)

 

Feuerer, M. ; Hill, J. ; Kretschmer, K. ; von Boehmer, H. ; Mathis, D. ; Benoist, C. Genomic definition of multiple ex vivo Treg sub-phenotypes. Proc Natl Acad Sci U S A. 30; 107 (13):5919. (2010)

 

Nolting, J. ; Daniel, C. ; Stuelten, C. ; Li, P. ; Sucov, H. ; Kim, B.G. ; Letterio, J.J. ; Kretschmer, K. ; Kim, H.J. ; von Boehmer H. Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines. J Exp Med. 28; 206(10):2131. (2009)

 

Düber, S. ; Hafner, M. ; Krey, M. ; Lienenklaus, S. ; Roy, B. ; Hobeika, E. ; Reth, M. ; Buch, T. ; Waisman, A. ; Weiss, S.* ; Kretschmer, K.* Induction of B cell development in adult mice reveals the ability of bone marrow to produce B-1a cells. Blood. 114: 4960. (2009) *Shared senior authorship

 

Polansky, J.K.* ; Kretschmer, K.* ; Freyer, J. ; Floess, S. ; Baron, U. ; Garbe, A.I. ; Hamann, A. ; von Boehmer, H ; Huehn, J. DNA methylation controls foxp3 gene expression. Eur. J. Immunol. 38(6): 1654. (2008) *These authors contributed equally

 

Kretschmer, K. ; Apostolou, I. ; Verginis, P. ; von Boehmer, H. Regulatory T cells and antigen-specific tolerance. Chem Immunol Allergy. 94:8. (2008)

 

Marson, A.* ; Kretschmer, K.* ; Frampton, G.M. ; Jacobsen, E.S. ; Polansky, J.K. ; MacIsaac, K.D. ; Levine, S.S. ; Fraenkel, E. ; von Boehmer, H. ; Young, R.A. Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature. 445(7130):931. (2007) *These authors contributed equally

 

Kretschmer, K. ; Heng, T.S.P. ; von Boehmer, H. De novo production of antigen specific suppressor cells in vivo. Nat. Protocols. 1(2):653. (2006)

 

Kretschmer, K. ; Apostolou, I. ; Jaeckel, E. ; Khazaie, K. ; von Boehmer, H. Making regulatory T cells with defined antigen specificity: Role in autoimmunity and cancer. Immunol. Rev. 212:163. (2006)

 

Kretschmer, K. ; Apostolou, I. ; Hawiger, D. ; Khazaie, K. ; Nussenzweig, M.C. ; von Boehmer, H. Inducing and expanding regulatory T cells by foreign antigen. Nat. Immunol. 6: 1219. (2005)

 

Contact

Group Leader

Prof. Dr. Karsten Kretschmer
karsten.kretschmer[at]crt-dresden.de


Assistant to Group Leader

Silvia Palme
silvia.palme[at]crt-dresden.de
Phone: +49 (0)351 458 82104