title: NK cell receptor NKp46 regulates graft-versus-host disease.
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 by immature 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.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel.
authors.forename: Hormas
authors.initials: H
authors.lastname: Ghadially
authors.affiliation: Hematology Division, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
authors.forename: Meir
authors.initials: M
authors.lastname: Ohana
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Elboim
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel.
authors.forename: Roi
authors.initials: R
authors.lastname: Gazit
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel.
authors.forename: Chamutal
authors.initials: C
authors.lastname: Gur
authors.affiliation: Hematology Division, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel. Electronic address: oferm@ekmd.huji.ac.il.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse