DECIPHERING THE ROLE OF TRIB1 IN REGULATORY T CELLS

Objectif

The role of regulatory T cells (Tregs) is crucial to maintain immune homeostasis by controlling peripheral tolerance. A better understanding in the molecular mechanisms involved in the biology of these Treg cells could improve their expansion and selection to treat immune-related diseases, achieve immunosuppression-free organ transplantation and to specifically target them in cancer. We reported on the over-expression of Tribbles-1 (TRIB1) in Tregs compared to their counterpart naïve T cells and that TRIB1 interacts with the master molecule of Tregs, FOXP3, a transcription factor essential for Treg suppressive activity. These results suggest still non explored potential links between TRIB1 in Tregs biology. Our goal is thus to decipher the role of TRIB1 in the Treg homeostasis and functions, through 3 main axes: 1) deciphering the function of TRIB1 in Tregs in vitro, 2) highlighting its implication in vivo using a combinaison of immune-related models and 3) discovering the signalling pathway of TRIB1 in Tregs. These results would not only increase TRIB1 mechanistic knowledge but also increase comprehension of Treg biology and bring opportunities to identify new strategies to modulate Tregs for immunotherapy.