By generating transgenic mice where an autologous NKG2D-ligand, Rae-1, could be upregulated on keratinocytes by administration of doxycycline it was shown that even in the absence of any overt microbial stress (or overt tissue/cellular dysregulation as in a tumor setting) engagement of NKG2D on the epidermal IELs (DETCs) activated these cells and caused profound changes in the local immune compartment (114). The gene discussed is KLRK1; the disease is neoplasm.