Involvement of the activating receptor NKG2D in cutaneous hypersensitivity drug reactions

Background Type IV drug hypersensitivity reactions with cutaneous manifestations (cADR) are highly variable in clinical appearance and degree of severity, ranging from maculopapular exanthema (MPE) to more severe disorders such as DRESS or SJS/TEN. Recent studies show NKp46+ cells in skin of drug-induced exanthemas, and NK cells expressing granulysin have been found in blister fluids from SJS/TEN patients, suggesting that NK cells can contribute to keratinocyte killing as well as CTLs. The balance of activating and inhibitory signals delivered by innate NK receptors determines the activity of NK cells. Among activating receptors, NKG2D is expressed in the cell membrane of NK cells and CTLs as a homodimer associated to the molecule DAP-10, which transduces the activating signal through the activation of PI-3 kinase. NKG2D ligands are HLA class I-like molecules MICA and MICB, and UL-16 binding proteins (ULBP). Their expression is upregulated in stress conditions.