Immunosuppressive function of NFATc1 in the intestinal tuft cell-immune crosstalk controlling helminth infection – TUFTREG

The intestinal epithelium, constituted of a single cell layer, represents the only border with the hostile environment in the gut lumen, containing foreign organisms and other toxic compounds. Maintenance of homeostasis requires crosstalk between the epithelium and the immune system, both at the steady state and during immune responses. We recently discovered the function of intestinal tuft cells in the initiation of type 2 immune responses following infection with helminth parasites. This tuft cell-mediated response is critical as worm expulsion is compromised in mice which are lacking tuft cells. However, most natural parasites have co-evolved with their hosts to develop strategies that dampen host immunity, thereby improving their survival. In this project, we will explore a novel regulatory circuit in tuft cells that is targeted by helminth parasites to inhibit type 2 immune responses. This study, using both in vivo and ex vivo models, will allow us to decipher the pathways via which helminths avert immune rejection. The identification of these mechanisms may be exploited to develop innovative therapies for patients with type2-induced diseases, including allergies and chronic inflammatory bowel diseases.