Transforming Growth Factor Beta (TGF-β) is a key regulatory cytokine of the immune system. Its deprivation leads to massive activation of the immune system and auto-immunity touching numerous organs. Interestingly, this cytokine is also largely expressed by the tumor-cell micro-environment and blocks immune system activation around the tumor, allowing tumor-cells to escape immuno-surveillance and be maintained. Thus, to understand the mechanisms by which TGF-β regulates the auto-reactivity of the immune system, it is essential to improve our knowledge of control of tumor-growth by the immune system.
Our work revealed that T lymphocytes are the main target-cells of TGF-β regulatory effects. We demonstrated that TGF-β signaling in T lymphocytes represses their reactivity against self-antigens, and blocks their cytotoxic and pro-inflammatory differentiation programs.
Bone junction infiltrated by T lymphocytes in the absence of signal given by TGF-b . Histology observation mimics polyarthritis.
Based on our previous observations, using powerful tools that we recently developed, our team studies the cellular and molecular mechansims by which TGF-β controls T lymphocyte tolerance to self-antigens. We pay particular attention to sub-populations of T lymphocytes known for being either regulatory or activator cells of the immune system. These fundamental research approaches are complemeted by pre-clinical studies on human samples allowing us to confirm our observations and propose potential clinical applications of our work.