T cell signaling

The immune system protects our bodies against invasion by pathogens of viral, bacterial, fungal and parasitic origin and against growth of neoplastic cells. The intensity of the adaptive immune responses must be tightly regulated in terms of class and duration to allow the proper production of immune-regulatory cytokines or chemokines by T lymphocyte subsets and the differentiation of B cells. Particularly CD4+ `helper` T (Th) cells face the challenge of balancing stability and plasticity in their gene expression programs as they differentiate into their specialized as e.g. Th1, Th2, Th17, Tfh, or iTreg subsets.


Nuclear receptors

Family members of the steroid/thyroid hormone family are well known for sensing external cues in order to regulate the expression of specific genes thereby controlling immune reaction of the organism. We discovered a critical function of NR2F6 as a potent and selective repressor of pro-inflammatory cytokine transcription and autoimmune disorders.
The focus of our lab is to understand how the NR signaling network is coupled to the T cell receptor (TCR) signaling cascade in order to enable selective interference during disease triggering immune responses as a long term perspective.


NR2F6 regulates autoimmune responses

Despite extensive linking of nuclear receptor function with specific CD4 T helper subsets, research on the functional roles and mechanisms of specific NRs in CD4 follicular T helper cells (Tfh) and germinal center (GC) B cells during the germinal center reaction is just emerging. We investigate how NR regulate specific cell types of the GC response and their implications for autoimmune diseases such as systemic lupus erythematosus (SLE) and multiple sclerosisbetween intestinal epithelial cells, the immune system and the microbiota is an area of active research.

 

 

 


Gastrointestinal inflammation and cancer

The immunological challenge of how to discriminate self from non-self is particularly complex at the intestinal mucosa. Immune cells have to discriminate between harmless food antigens, antigens derived from the microbiota and pathogens and their toxins. Within the gastrointestinal tract, nuclear receptors are targets of numerous naturally occurring and man-made compounds, such as hormones, lipids and vitamins and therefore play fundamental roles in both epithelial intestinal cell integrity and intestinal immune cell differentiation and function.

How nuclear receptors regulate gut homeostasis in the complex interplay between intestinal epithelial cells, the immune system and the microbiota is an area of active research.