Increased serum NKG2D-ligands and downregulation of NKG2D in peripheral blood NK cells of patients with major burns

Josef Haik, Gil Nardini, Noga Goldman, Gilli Galore-Haskel, Moti Harats, Isaac Zilinsky, Oren Weissman, Jacob Schachter, Eyal Winkler, Gal Markel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)2220-2228
Number of pages9
JournalOncotarget
Volume7
Issue number3
DOIs
StatePublished - 2016

Keywords

  • Burns
  • Immune response
  • Immune suppression
  • Immunity
  • Immunology and Microbiology Section
  • Lysis receptors
  • MICB
  • Natural killer

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