Modulation of immune checkpoint signaling in the context of central nervous system inflammation – Control-CHECK

The inopportune stimulation of immune checkpoints (IC) can lead to a temporary silencing of the immune system, which can be deleterious in pathological situations such as infections or cancers. The biological mechanisms controlling the activity of these receptors are still unclear to this day. We have identified a new regulator of IC, which acts as a molecular brake of the inhibitory signals transmitted by those receptors. We propose here to elucidate the mechanisms by which this regulator represses IC and to analyze the consequences of this regulation in models of central nervous system autoimmunity. We will also study the importance of this mechanism in the susceptibility to immunotherapy targeting IC and in the phenomenon of inter-individual variations observed in response to those treatments. This study should shed an original light on the biology of IC whose discovery has recently boomed the field of immunotherapy applied to cancers and autoimmune diseases.