Journal article

A point mutation in the Ncr1 signal peptide impairs the development of innate lymphoid cell subsets

Francisca F Almeida, Sara Tognarelli, Antoine Marcais, Andrew J Kueh, Miriam E Friede, Yang Liao, Simon N Willis, Kylie Luong, Fabrice Faure, Francois E Mercier, Justine Galluso, Matthew Firth, Emilie Narni-Mancinelli, Bushra Rais, David T Scadden, Francesco Spallotta, Sandra Weil, Ariane Giannattasio, Franziska Kalensee, Tobias Zoeller Show all

ONCOIMMUNOLOGY | TAYLOR & FRANCIS INC | Published : 2018

Abstract

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 Ly5.1..

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Grants

Awarded by National Health and Medical Research Council Australia


Awarded by LOEWE Center for Cell and Gene Therapy Germany


Awarded by European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme


Awarded by ANR


Awarded by fondation ARC


Awarded by European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (TILC)


Awarded by GO-IN post-doc fellowship at the University Frankfurt Germany


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council Australia [1054925]; and the National Health and Medical Research Council Australia [1124907]. E.U. lab has been supported by the LOEWE Center for Cell and Gene Therapy Germany [III L 4-518/17.004]. S.U. lab is supported by funding form the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme under grant agreement No 648768; from the ANR (No ANR-14-CE14-0009-01) and from the fondation ARC (No PGA120140200817). E.V. lab is supported by funding form the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (TILC, grant agreement No 694502); the Agence Nationale de la Recherche; Equipe Labellisee "La Ligue," Ligue Nationale contre le Cancer, MSDAvenir, Innate Pharma and institutional grants to the CIML (INSERM, CNRS, and Aix-Marseille University) and to Marseille Immunopole. S.T. received a GO-IN post-doc fellowship at the University Frankfurt Germany [PCOFUND-GA-2011-291776] and by the Madeleine Schickedanz-KinderKrebs-Stiftung; W.S. is supported by a Walter and Eliza Hall Institute Centenary Fellowship sponsored by CSL Limited. S.N.W. was supported by a Walter and Eliza Hall Trust Centenary Fellowship.