ZMB Member Elke Cario, Research
The intestinal epithelial cell (IEC) layer serves as an important defensive barrier of the mucosal immune system that forms a bipolar interface between the vast variety of commensals and other antigens of the lumen and subjacent immune cells present in the lamina propria. The intestinal epithelium consists of four lineages of differentiated cells (enterocytes, goblet cells, Paneth cells, enteroendocrine cells), - all of which arise from stem cells residing in the intestinal crypt. Commensal-induced innate immune signalling drives essential IEC functions that help in maintaining mucosal equilibrium. Any disturbance or imbalance in innate immune signalling may lead to intestinal disorders, yet these mechanisms are so far poorly understood.
My lab studies the role and regulation of the intestinal epithelium in health and disease. Numerous gastrointestinal diseases (such as inflammatory bowel diseases, pathogenic infections, colon cancer, radiation/chemical damage) target these frontline cells and affect IEC survival, proliferation, restitution, differentiation and cell-cell communication. Increased intestinal permeability due to IEC barrier dysfunction may trigger bacterial translocation, thus promoting other organ manifestations of disease (e.g. gut-liver-axis).
We focus on delineation of the functional interrelations of innate immune signaling in IEC physiology and pathophysiology. Our goal is to define the complex mechanistics and functional diversity of IEC innate immunity and determine how this apparatus shapes mucosal homeostasis of the intestine. Our aim is to identify related signaling targets that may offer novel therapeutic approaches in the treatment of major gastrointestinal disorders, including inflammatory bowel diseases and cancer. For example, we have recently shown that a TLR2 agonist controls acute mucosal inflammation by conferring tight-junction-associated IEC barrier protection.
We use both human and murine in-vitro and ex-vivo systems to model IEC biology and its interactions with the environment. In addition, we use murine in-vivo models of acute intestinal injuries and chronic spontaneous colitis in combination with genetic and pharmacologic manipulations to test hypotheses about IEC and related mucosal function and systemic consequences. We translate our results to human disease through the use of ileal/colonic biopsies and other specimens obtained from GI patients. One further interest involves morphological characterization of subcellular (re)distribution of immune signaling components in IEC (confocal laser 3D-reconstruction).