Molecular and Cellular Immunology/Focus Immune Regulation
Previous and Current Research
CD4+ regulatory T (Treg) cells expressing the forkhead box transcription factor Foxp3 have a vital function in the maintenance of immune homeostasis and the prevention of fatal multi-organ autoimmunity throughout life. In the last decade, Foxp3+ Treg cells have raised the hope for novel cell-based therapies to achieve tolerance in clinical settings of unwanted immune responses such as autoimmunity and graft rejection. Conceptually, the antigen-specific enhancement of Treg cell function is of particular importance because such strategies will minimize the requirements for pharmaceutical immunosuppression, sparing desired protective host immune responses to infectious and malignant insults. In this context, our research interests focus on molecular and cellular pathways that govern the generation, lifestyle and suppressor function of Foxp3+ Treg cells.
Future Projects and Goals
- Foxp3+ Treg cells as gain-of-function targets in autoimmunity and transplantation
- Cell signaling and epigenetics in Foxp3+ Treg cell biology
- Transcription regulation in tolerance and autoimmunity (incl. miRNAs)
- Mechanisms of suppression by Foxp3+ Treg cells
Methodological and Technical Expertise
- Mouse models of human autoimmune diseases (IPEX, diabetes, rheumatoid arthritis, multiple sclerosis)
- Mouse molecular genetic tools (immune deficient mice, Cre recombinase transgenic mice etc.)
- Flow cytometry and fluorescent activated cell sorting (FACS)
- Experimental in vitro and in vivo approaches to study the biology of T cells
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. 2014. 44(12):3632–45.
Riewaldt J, Düber S, Boernert M, Krey M, Dembinski M, Weiss S, Garbe AI, Kretschmer K.
Severe developmental B lymphopoietic defects in Foxp3-deficient mice are refractory to adoptive regulatory T cell therapy.
Front Immunol. 2012. 3:141.
Petzold C, Schallenberg S, Stern JNH, Kretschmer K.
Targeted antigen delivery to DEC-205+ dendritic cells for tolerogenic vaccination.
Rev Diabet Stud. 2012; 9(4):305.
Schallenberg S, Tsai PY, 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. 2010. 207(7):1393.
Kretschmer K, Apostolou I, Hawiger D, Khazaie K, Nussenzweig MC, von Boehmer H.
Inducing and expanding regulatory T cells by foreign antigen.
Nat. Immunol. 2005. 6: 1219.