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To mount a secondary immune response, dendritic cells must process antigens, migrate to lymph nodes and form synapses with T cells. Critical to 3D migration and mechano-sensing is the nucleus, which is the size-limiting barrier for navigation through gaps in the extracellular matrix. Here, we show that spherical deformations of the dendritic cell nuclear membrane occur following inflammatory activation, as a partial result of reduced cell adhesion. By re-programming the nucleus, dendritic cells are less confined by complex 3D environments and can overcome the typical 2 – 3-micron pore limit for migration. Nuclear deformation is concomitant with the redistribution and bundling of perinuclear actin away from the nucleus, reducing force across Nesprin-2G based linker of nucleoskeleton and cytoskeleton (LINC) complexes. Furthermore, through phosphoproteomics, we connect this nuclear deformation to cofilin-1 serine 41 phosphorylation. This phosphorylation further drives nuclear deformation and bundles cofilin-1 with F-actin into a peri-nuclear halo-shaped micro-domain. In summary, these data describe novel signaling events through which dendritic cells deform their nucleus to enhance their migratory capacity; a molecular event that may be re-capitulated in other contexts such as wound healing and cancer.