title: Increased serum NKG2D-ligands and downregulation of NKG2D in peripheral blood NK cells of patients with major burns.
abstract: Immune suppression following major thermal injury directly impacts the recovery potential. Limited data from past reports indicate that natural killer cells might be suppressed due to a putative soluble factor that has remained elusive up to date. Here we comparatively study cohorts of patients with Major and Non-Major Burns as well as healthy donors. MICB and ULBP1 are stress ligands of NKG2D that can be induced by heat stress. Remarkably, serum concentration levels of MICB and ULBP1 are increased by 3-fold and 20-fold, respectively, already within 24h post major thermal injury, and are maintained high for 28 days. In contrast, milder thermal injuries do not similarly enhance the serum levels of MICB and ULBP1. This kinetics coincides with a significant downregulation of NKG2D expression among peripheral blood NK cells. Downregulation of NKG2D by high concentration of soluble MICB occurs in cancer patients and during normal pregnancy due to over production by cancer cells or extravillous trophoblasts, respectively, as an active immune-evasion mechanism. In burn patients this seems an incidental outcome of extensive thermal injury, leading to reduced NKG2D expression. Enhanced susceptibility of these patients to opportunistic viral infections, particularly herpes viruses, could be explained by the reduced NKG2D expression. Further studies are warranted for translation into innovative diagnostic or therapeutic technologies.
authors.affiliation: Department of Plastic Surgery, Tel Aviv University, Tel Aviv, Israel.|Talpiot Medical Leadership Program, Tel Aviv University, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Josef
authors.initials: J
authors.lastname: Haik
authors.affiliation: Department of Plastic Surgery, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Nardini
authors.affiliation: Department of General Surgery C, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Noga
authors.initials: N
authors.lastname: Goldman
authors.affiliation: Ella Institute of Melanoma, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Gilli
authors.initials: G
authors.lastname: Galore-Haskel
authors.affiliation: Department of Plastic Surgery, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Moti
authors.initials: M
authors.lastname: Harats
authors.affiliation: Department of Plastic Surgery, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Isaac
authors.initials: I
authors.lastname: Zilinsky
authors.affiliation: Department of Plastic Surgery, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Weissman
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Ella Institute of Melanoma, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Schachter
authors.affiliation: Department of Plastic Surgery, Tel Aviv University, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Winkler
authors.affiliation: Talpiot Medical Leadership Program, Tel Aviv University, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Ella Institute of Melanoma, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Markel
mesh_terms: D000328:Adult; D002056:Burns / Q000097:blood / Q000276:immunology / Q000473:pathology*; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000096:biosynthesis / Q000276:immunology*; D009369:Neoplasms / Q000378:metabolism; D009894:Opportunistic Infections / Q000276:immunology; D055815:Young Adult
chemical_list: D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; C423231:ULBP1 protein, human
keywords: Immune response; Immunity; Immunology and Microbiology Section; MICB; burns; immune suppression; lysis receptors; natural killer