Immune cells experience large deformation events while paroling their environment. These cell shape changes arise from the continuous physical constraints encountered during migration within tissues and organs. It has become increasingly clear that these cells can survive and adapt to changes in cell shape using dedicated shape-sensing pathways. However, how shape sensing impacts their behavior and function remains largely unknown. During my seminar, I will show unpublished data highlighting that the nuclear shape changes experienced by immune cells define their migratory behavior and immunoregulatory properties, revealing the contribution of the physical properties of tissues to tuning of the balance between tolerance an immunity.