Research Papers: Immunology:

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 and Gal Markel _

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Oncotarget. 2016; 7:2220-2228. https://doi.org/10.18632/oncotarget.6789

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Josef Haik1,2,3, Gil Nardini1, Noga Goldman4, Gilli Galore-Haskel5, Moti Harats1, Isaac Zilinsky1, Oren Weissman1, Jacob Schachter3,5, Eyal Winkler1,3 and Gal Markel2,3,5

1 Department of Plastic Surgery, Tel Aviv University, Tel Aviv, Israel

2 Talpiot Medical Leadership Program, Tel Aviv University, Tel Aviv, Israel

3 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

4 Department of General Surgery C, Tel Aviv University, Tel Aviv, Israel

5 Ella Institute of Melanoma, Sheba Medical Center, Ramat Gan, Israel

Correspondence to:

Gal Markel, email:

Keywords: burns, immune suppression, natural killer, lysis receptors, MICB, Immunology and Microbiology Section, Immune response, Immunity

Received: September 26, 2015 Accepted: December 23, 2015 Published: December 29, 2015


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.

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