Helmholtz University Junior Research Group Immune Tolerance

Dr. Markus Feuerer

Immune cells infiltrate and destroy insulin producing islet cells in the pancreas
© dkfz.de

The immune system has evolved over time to defeat external threats such as bacteria and viruses as well as internal threats like cancer. The ability of the immune system to destroy such a diverse number of foreign invaders is a tribute to its flexibility. However, this comes at a price and the complexity can lead to severe autoimmune diseases. In addition, misguided or deregulated immune responses have recently been implicated in non-classical immune disorders such as obesity. To minimize such collateral damage, powerful mechanisms of immune tolerance have evolved to keep unwanted immune responses at bay. These mechanisms must be tightly controlled as overactive immune tolerance can specifically counteract desirable immune reactions (e.g. anti-tumor or anti-microbial).
Peripheral immune regulation is maintained by specialized cells, including T cells and myeloid-derived cells. The ability to actively suppress an immune response makes regulatory T (Treg) cells important elements to consider. Treg cells are a specialized lineage of CD4+ T cells, characterized by expression of the transcriptional regulator Foxp3. Treg cells are essential for the maintenance of self-tolerance.
Our goal is to explore Treg cell biology in the context of autoimmunity and anti-tumor-immunity. What are the molecules behind these specialized cells? In addition, we are interested in the local microenvironment critically involved in immune regulation, especially the innate immune axes.

Harnessing the potential of Treg cells is one of the most promising new approaches to control immune function and treat autoimmune diseases and cancer. However, future strategies to bring Treg-based therapies into the clinics will rely on a better understanding of the molecular pathways that control the development and function of Foxp3+ Treg cells.
Peripheral immune regulation is not only maintained by adoptive immune cells but also by innate cells such as myeloid cells. Innate cells are believed to be the earliest cells activated and recruited to a site of inflammation. Thus, signals integrated and released by these early witnesses will crucially influence the overall response to the challenge.

As a second main project, we are focusing on understanding the role that myeloid cells play in immune regulation. Myeloid cells are a heterogeneous group of cells involved at the interface of inflammation and wound-healing. Some members promote inflammation whereas others have suppressive or regulatory functions. We are especially interested in investigating how monocytes and their progenies (monocyte-derived-DCs and -macrophages) can contribute to inflammation or productive immunity on one hand and tolerance or tissue repair on the other. How is their relationship to inflammation that promotes cancer formation or progression?

Contact

Dr. Markus Feuerer
Immune Tolerance (D100)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 1530

Selected Publications

  • Feuerer M, Shen Y, Littman D, Benoist C, Mathis D (2009). How punctual ablation of Foxp3+ T cells unleashes an autoimmune lesion within the pancreas islets. Immunity, 31, 654-64.
  • Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine AB, Benoist C, Shoelson S, Mathis D (2009). Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nature Medicine,15, 930-9.
  • Hettinger J, Richards DM, Hansson J, Barra BB, Joschko AC, Krijgsveld J and Feuerer M. Origin of monocytes and macrophages from a committed progenitor. Nature Immunology 2013 Aug;14(8):821-30
  • Cipolletta D. et al. (2012). PPAR-y is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature, 486(7404): 549-53.
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