NK Cell Receptor NKp46 Regulates Graft-versus-Host Disease

Hormas Ghadially, Meir Ohana, Moran Elboim, Roi Gazit, Chamutal Gur, Arnon Nagler, Ofer Mandelboim

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Hematopoietic stem cell transplantation (HSCT) is often the only curative treatment for a wide variety of hematologic malignancies. Donor selection in these diseases is crucial, given that transplanted cells can mediate not only the desired graft-versus-leukemia effect but also graft-versus-host disease (GVHD). Here, we demonstrate that in the absence of NKp46, a major killer receptor expressed by human and mouse natural killer (NK) cells, GVHD is greatly exacerbated, resulting in rapid mortality of the transplanted animals because of infection with commensal bacteria. Furthermore, we demonstrate that the exacerbated GVHD is the result of an altered ability of immune cells to respond to stimulation byimmature dendritic cells. Because high and low expression of NKp46 on NK cells is observed in different individuals, our data indicate that choosing NKp46-high donors for the treatment of different hematologic malignancies might lead to better tumor eradication while minimizing GVHD.

Original languageEnglish
Pages (from-to)1809-1814
Number of pages6
JournalCell Reports
Volume7
Issue number6
DOIs
StatePublished - 26 Jun 2014
Externally publishedYes

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