Crohn's & Colitis Focus Group

The progress in understanding the mechanisms of T-cell trafficking, migration and homing, as well as towards the development of mechanisms for the inactivation of these events have been translated into treatment strategies of autoimmune diseases. Our ongoing studies focus on the analysis of pathways that restrict homing of T cell homing, and thereby fine-tune the immune response at specific lymphoid and peripheral tissues. We characterized two pathways that limit T cell migration impairing of lymphocyte homing to peripheral lymph nodes resulting in attenuated progression of inflammation like in various models, including IBD. We now focus on key molecules involved in this homing regulation, in an attempt to develop reagents that will block their function. 

The Sorek laboratory studies the dynamics of phage attacks and phage resistance among bacteria that inhabit the human gut in Crohn/IBD and normal patients. The team is testing the hypothesis that part of the shift in the gut microbial population that is observed in IBD patients, is connected to bacteriophages that attack gut bacteria.

Runx3 transcription factor is a key hematopoietic gene expression regulator. In the murine gastrointestinal tract (GIT) Runx3 is highly expressed in leukocytes but not in the GIT epithelium. Previously, we found that Runx3-/- mice spontaneously develop inflammatory bowel disease (IBD) and have shown that Runx3 is required for the development and function of dendritic cells (DC). Given that DC play crucial role in mucosal immunity we have generated DC^Runx3-/- mice and demonstrated that these mice develop IBD with characteristics similar to those observed in Runx3-/- mice. We thus established DC^Runx3-/- mice as an attractive and highly specific model recapitulating the hallmarks of human IBD underscoring the importance of Runx3 in DC-mediated GIT homeostasis. We currently use the DC^Runx3-/- mouse model to elucidate the molecular mechanisms underlying IBD development due to lack of Runx3 in lamina propria DC.