title: Soluble MICA-NKG2D interaction upregulates IFN-γ production by activated CD3-CD56+ NK cells: potential impact on chronic graft versus host disease.
abstract: A soluble isoform of MHC class I chain-related molecule A (soluble MICA), generated by proteolytic shedding from the membrane-bound MICA of various tumor cells, has been shown to downregulate both the expression of natural killer group 2-member D receptor and the cytotoxic function of effectors cells and was postulated as a mechanism for tumor immune evasion. Its effect on the expression of cytokines by the effector cells remained unexplored. Here we demonstrate that the sMICA molecules upregulate interferon gamma expression by interleukin-12/interleukin-18-activated CD3(-)CD56(+) natural killer cells, witnessing the pro-inflammatory effect of soluble MICA. Overall, these data are in line with our previous observations that the raised serum levels of soluble MICA, following allogeneic hematopoietic stem cell transplantation, confer susceptibility to and the presence of pre-transplantation anti-MICA antibodies in the patient's serum confer protection against chronic graft versus host disease.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS-940, F-75010 Paris, France.
authors.forename: Wahid
authors.initials: W
authors.lastname: Boukouaci
authors.forename: Reem
authors.initials: R
authors.lastname: Al-Daccak
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dulphy
authors.forename: Laura
authors.initials: L
authors.lastname: Lauden
authors.forename: Kahina
authors.initials: K
authors.lastname: Amokrane
authors.forename: Catherine
authors.initials: C
authors.lastname: Fortier
authors.forename: François
authors.initials: F
authors.lastname: Marzais
authors.forename: Meriem
authors.initials: M
authors.lastname: Bennabi
authors.forename: Regis
authors.initials: R
authors.lastname: Peffault de Latour
authors.forename: Gerard
authors.initials: G
authors.lastname: Socie
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Krishnamoorthy
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
mesh_terms: D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D002908:Chronic Disease; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D007371:Interferon-gamma
keywords: IFN-γ; IL; MHC class I chain-related molecule A; MICA; NK; NKG2D; allo-HSCT; allogeneic hematopoietic stem cell transplantation; cGvHD; chronic graft versus host disease; interferon gamma; interleukin; mbMICA; membrane-bound MICA; natural killer; natural killer group 2-member D; sMICA; soluble MICA