With regard to IFI16, it is conceivable to hypothesize that the previously described over- or aberrant expression and mislocalization of this nuclear protein, earlier in the cytoplasm and later on in the extracellular milieu, might lead to loss of tolerance and development of anti-IFI16 antibodies, as demonstrated in skin lesions from SLE patients and in keratinocytes cultured in vitro under conditions of UVB light-induced cell injury (104). Here, IFI16 is linked to systemic lupus erythematosus.