Systemic delivery of αGalCer/CD1d-NPs was able to comprehensively blunt spontaneous and experimental liver autoimmunity in various genetic backgrounds, consistent with a robust immunoregulatory activity of the locally re-programmed LiNKTR1 cells that is dissociated from disease type (PBC vs. AIH) and genetic background (C57BL/6 vs. NOD.c3c4). Here, CD1D is linked to primary biliary cholangitis.