My research team seeks to understand the mechanisms leading to tissue specific immunity. This is the concept that the innate and adaptive immune systems are tailored to the organ they reside in, in order to best support the immunological needs of each tissue. These include protection from pathogen invasion or autoimmunity but also for example supporting tissue regeneration after injury. However, we also postulate that this immune specialization and compartmentalization underlie the nature and site specificity of disease susceptibility, such as vulnerability to pathogens, allergies, autoimmunity, chronic inflammatory diseases and cancers, and that insight into how the immune system is wired in each niche will permit more fitted and potentially effective therapeutic strategies. While this idea applies to all organs, we study primarily the digestive system, that is the gut, liver-biliary system and pancreas. Our main project areas encompass:

1. Pinpointing the critical driving forces and target cells that make lymph nodes unique and matched to the organ they drain. Lymph nodes are placed throughout the body and, because each lymph node drains a restricted area, the anatomical sites in which tissue specific adaptive immunity is initiated. We recently discovered that the gut draining lymph nodes are not only compartmentalized but also distinct in their default immune tone, favoring tolerance in the upper small intestine but inflammation in the colon. Building on this finding, we investigate what cell types and external stimuli are responsible for these immune signatures. This includes considering both immune cells such as dendritic cells and non-immune cells such as the lymphatic vasculature and other stromal cells as subject to modulation by environmental queues like the gut microbiome or dietary components. A better understanding of what the immune properties of each lymph node in the body are and how they come about could be harnessed in the future to devise organ specific or more efficient immunomodulatory therapies.

2. Investigating the intestinal and hepatic influence on pancreatic innate and adaptive immunity. One “driving force” for a tissue’s immune landscape can be its connection to another organ. The gut is increasingly recognized as a source of immunomodulatory signals that can reach very distant tissues such as the heart or brain, however we investigate how the much more intimate connection between the pancreas, liver and gut shape pancreatic immunity: Due to the common developmental origin, the three organs share lymph nodes, ducts and vasculature. We therefore postulate that they not only communicate to coordinate digestion and nutrient uptake but also their immune systems. Our insights enable us to better understand -and potential prevent or reverse- the etiology of immunopathologies like type 1 diabetes, chronic pancreatitis or pancreatic cancer.

Techniques used

We use a wide range of techniques in mice, including lymph node dissection, microsurgery, lymphatic vessel cannulation, pancreatic islet isolation, multimodal imaging, single cell gene expression analysis, gnotobiotics, and genetic manipulation of mice to model diseases or track immune events. We use a spectrum of gastrointestinal pathogens, and study human material to relate our work to human disease.