Burkhard Becher

Institute Experimental Immunology, Department Pathology, University Hospital of Zurich, Switzerland

Title: Th17 derived factors: the target organ matters

Abstract:

Over the past 20 years the importance of TH1 cells and TH1-inducing cytokines were studied in autoimmune disease and it was widely held that TH1 cells are the culprits behind the autoimmune attack against tissues. Even though the loss of major TH1 cytokines did not prevent the development of tissue inflammation, the central function of IL-12 and IL-18 in autoimmunity and their role as TH1-inducing cytokines kept the notion that TH1 cells are responsible for autoimmunity solidly in place. We and others provided the basis for a paradigm shift and the discovery that a close relative of IL-12, IL-23 is in fact the key player in EAE. IL-23 was subsequently found to drive the polarization of a new T helper cell subset coined TH17 cells.

To study the actual impact of IL-17 on CNS inflammation, we generated transgenic mice in which high levels of expression of IL-17A could be initiated after cre-mediated recombination. Although ubiquitous overexpression of IL-17A led to epithelial inflammation and granulocytosis, T cell–specific IL-17A overexpression did not have a perceptible impact on the development and health of the mice. In the context of EAE, neither the T cell–driven overexpression of IL-17A nor its complete loss had a major impact on the development of clinical disease. Since IL-17F may be able to compensate for the loss of IL-17A, we also generated IL-17F–deficient mice. This strain was fully susceptible to EAE and displayed unaltered emergence and expansion of auto-reactive T cells during disease. IL-22, another major TH17 cytokine also does not contribute to the development of EAE in gene-targeted mice. By systematically studying the role and function of TH17 signature cytokines in autoimmune disease in mice, we could demonstrate that they are powerful mediators of tissue inflammation in several organs (including the skin and lung), surprisingly however with the exception of the nervous system. Taken together with other recent reports which question the role of TH17 cells in autoimmune diseases, I will discuss the concept of TH1, TH17 cells and their produced factors as culprits behind autoimmune inflammation and the critical function of the target tissue of inflammation.

Biography:

Burkhard Becher studied Biology at the University of Cologne in Germany and specialized in Molecular Genetics and Biochemistry.

In 1995, for his graduate studies he went to the Montreal Neurological Inst. at Mc Gill University in Canada to learn Neuroimmunology with Jack Antel.  His work focused on the role of microglia cells as brain-resident myeloid cells capable of instructing self-reactive T cells in the context of autoimmune neuroinflammation. There, he described the T cell/microglia interface and learned about cytokine networks and T cell/APC interactions.

In 1999 he joined the lab of Randy Noelle at the Dartmouth Medical School to extend his work to in vivo models and transgenic mice. He developed tools to specifically manipulate microglial cells in vivo during inflammation.

In 2003, he was recruited as Assistant Professor to the Neurology Department at the University Hospital of Zurich, where he continued to work on the question as to how brain-antigen-reactive T cells recognize their target antigen in the brain. In contrast to expectations that microglia (his favorite cell type) would serve this purpose, his team discovered that brain-vessel associated dendritic cells are the first and only required Antigen-presenting cells permitting T cells to cross the blood-brain barrier and to commence inflammation.

In 2008, he obtained the prestigious position as chair of the Institute of experimental Immunology (prior held by Rolf Zinkernagel), where he continues to study Autoimmunity, Tumor Immunology and Cytokine Biology.

Burkhard is also a passionate father, hobby-cook and sailor.