TY - JOUR A1 - Almeida, Francisca F. A1 - Tognarelli, Sara A1 - Marçais, Antoine A1 - Kueh, Andrew J. A1 - Friede, Miriam Elisabeth A1 - Liao, Yang A1 - Willis, Simon N. A1 - Luong, Kylie A1 - Faure, Fabrice A1 - Mercier, Francois E. A1 - Galluso, Justine A1 - Firth, Matthew A1 - Narni-Mancinelli, Emilie A1 - Rais, Bushra A1 - Scadden, David T. A1 - Spallotta, Francesco A1 - Weil, Sandra A1 - Giannattasio, Ariane A1 - Kalensee, Franziska A1 - Zöller, Tobias A1 - Huntington, Nicholas D. A1 - Schleicher, Ulrike A1 - Chiocchetti, Andreas G. A1 - Ugolini, Sophie A1 - Herold, Marco A1 - Shi, Wei A1 - Koch, Joachim A1 - Steinle, Alexander A1 - Vivier, Eric A1 - Walzer, Thierry A1 - Belz, Gabrielle T. A1 - Ullrich, Evelyn T1 - A point mutation in the Ncr1 signal peptide impairs the development of innate lymphoid cell subsets T2 - OncoImmunology N2 - NKp46 (CD335) is a surface receptor shared by both human and mouse natural killer (NK) cells and innate lymphoid cells (ILCs) that transduces activating signals necessary to eliminate virus-infected cells and tumors. Here, we describe a spontaneous point mutation of cysteine to arginine (C14R) in the signal peptide of the NKp46 protein in congenic Ly5.1 mice and the newly generated NCRB6C14R strain. Ly5.1C14R NK cells expressed similar levels of Ncr1 mRNA as C57BL/6, but showed impaired surface NKp46 and reduced ability to control melanoma tumors in vivo. Expression of the mutant NKp46C14R in 293T cells showed that NKp46 protein trafficking to the cell surface was compromised. Although Ly5.1C14R mice had normal number of NK cells, they showed an increased number of early maturation stage NK cells. CD49a+ILC1s were also increased but these cells lacked the expression of TRAIL. ILC3s that expressed NKp46 were not detectable and were not apparent when examined by T-bet expression. Thus, the C14R mutation reveals that NKp46 is important for NK cell and ILC differentiation, maturation and function. KW - innate lymphoid cells KW - activation receptors KW - intracellular trafficking KW - congenic mice Y1 - 2018 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47672 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-476723 SN - 2162-402X SN - 2162-4011 N1 - Copyright © 2018 The Author(s). Published by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. VL - 7 IS - 10, e1475875 SP - e1475875-1 EP - e1475875-15 PB - Taylor & Franics CY - Abingdon ER -