Cytotoxic CD8+NKG2D+ T lymphocytes are the primary immunocytes that infiltrate the surroundings of HFs and are held to be the key cells that drive the disease pathogenesis NKG2D is an activating receptor expressed on CD8+ T cells and NK cells which recognize NKG2D ligands, like ULBP3/6 and MICA, and then upregulate MHC expression, which is crucial in mediating HP-IP collapse (64). This evidence concerns the gene MICA and Hand-foot syndrome.