Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Induction of NKG2D ligands by gamma radiation and tumor necrosis factor-alpha may participate in the tissue damage during acute graft-versus-host disease. 1836 Feb 76

The negative regulation of adaptive immunity is relevant to maintain lymphocyte homeostasis. Several studies on natural killer (NK) cells have shown a previously unappreciated immunomodulatory role, as they can negatively regulate T cell-mediated immune responses by direct killing and by secretion of inhibitory cytokines. The molecular mechanisms of T cell suppression by NK cells, however, remained elusive. Only in the last few years has it become evident that, upon activation, human T cells express MICA-B, ULBP1-3, and PVR, ligands of the activating receptors NKG2D and DNAM-1, respectively. Their expression renders T cells targets of NK cell lysis, representing a new mechanism taking part to the negative regulation of T cell responses. Studies on the expression of NKG2D and DNAM-1 ligands on T cells have also contributed in understanding that the activation of ATM (ataxia-telangiectasia, mutated)/ATR (ATM/Rad3-related) kinases and the DNA damage response is a common pathway regulating the expression of activating ligands in different types of cells and under different conditions. The functional consequences of NKG2D and DNAM-1 ligand expression on activated T cells are discussed in the context of physiologic and pathologic processes such as infections, autoimmunity, and graft versus host disease.
 ...
PMID:NKG2D and DNAM-1 activating receptors and their ligands in NK-T cell interactions: role in the NK cell-mediated negative regulation of T cell responses. 2331 96