Induction of NKG2D ligands by gamma radiation and tumor necrosis factor-alpha may participate in the tissue damage during acute graft-versus-host disease.
Immunopathology of acute graft-versus-host disease (aGVHD) involves secretion of proinflammatory cytokines with subsequent expression of danger signals by injured host tissues. This explanation, however, does not explain the cluster of aGVHD target organs (skin, gut, and liver). NKG2D ligands (MICA/B and ULBP1-3 proteins) are stress-induced molecules that act as danger signals to alert NK and alphabeta or gammadelta CD8 T cells through engagement of the activating NKG2D receptor. We observed a strong and reversible induction of MICA/B expression in skin and liver sections during aGVHD. Tumor necrosis factor-alpha and gamma-radiation up-regulated expression of MICA/B and ULBP proteins in vitro on skin and intestine epithelial cell lines and ex vivo in normal skin explants. This NKG2D-ligand induction was regulated by a complex interplay between NFkB and JNK activation pathways. Our data suggest that NKG2D ligand induction might participate in the amplification loop that leads to tissue damage during aGVHD.
Gannagé
Monique
M
Institut National de la Santé et de la Recherche Medicale (INSERM), U561, Hôpital St-Vincent de Paul, Paris, France.
Buzyn
Agnès
A
Bogiatzi
Sofia I
SI
Lambert
Marion
M
Soumelis
Vassili
V
Dal Cortivo
Liliane
L
Cavazzana-Calvo
Marina
M
Brousse
Nicole
N
Caillat-Zucman
Sophie
S
D000208:Acute Disease; D001706:Biopsy; D002460:Cell Line; D004847:Epithelial Cells / Q000502:physiology / Q000528:radiation effects; D058851:GPI-Linked Proteins; D005720:Gamma Rays; D006086:Graft vs Host Disease / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000528:radiation effects*; D012867:Skin / Q000166:cytology / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; C423230:ULBP2 protein, human