Projects
Adaptive Immune Regulation
The powerful armada of immune cells can eliminate numerous of invading pathogens, yet turn a blind eye to self-tissue. The thymus contributes during T cell differentiation by depleting self-reactive T cell clones. This central deletion is powerful, yet imperfect. Self-reactive T cells enter the periphery, and are responsible for many autoimmune diseases.
The immune system has evolved a second layer of peripheral tolerance mechanism to keep these “forbidden clones” as well as excessive or unwanted immune reactions under control. These regulatory mechanisms are of particular interest, since they impinge on many diseases or treatment strategies, including autoimmunity, anti-tumor-immunity, transplantation, and persistent infections. Especially, anti-tumor-immunity is strongly compromised by peripheral tolerance.
A specialized subset of CD4+ T cells, commonly termed regulatory T(reg) cells, are key players. They are characterized by the expression of the forkhead/winged helix transcription factor Foxp3.
This project will characterize molecular mechanisms involved in Treg cell biology. There is limited knowledge on how these specialized cells influence other adopotive or innate immune cells (e.g. NK cells) as well as non-immune cells. Different experimental systems are in place to test for function including relevant in vivo model systems such as autoimmune diabetes and spontaneous tumors
Innate Immune Regulation
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The myeloid monocyte-macrophage-dendritic cell (DC) - system is getting increasing attention in the last few years. With new markers such as Ly6C, CCR2 and Cx3CR1 the precursors-product relationship could be analyzed.
The recruitment of subpopulations of monocytes or macrophages/DCs derived thereafter can heavily influence the local inflammatory state in a giving tissue. Subsets of monocytes were associated with phagocytic and inflammatory functions whereas allied subsets had attenuated inflammatory properties and could promote wound healing and tissue repair. Very strong differences in subsets and function have been reported whether the primary inflammatory stimulus was a bacterial infection or a growing tumor.
Yet, still little is known about their effector mechanisms, plasticity, and the interactions with other immune cells.
The aim of this project is to characterize molecular targets of these innate players. How do these cells act during acute and chronic inflammation? How do they help to establish or break immune tolerance?
