title: Natural killer cell crosstalk with allogeneic human cardiac-derived stem/progenitor cells controls persistence.
abstract: OBJECTIVE
  Allogeneic human cardiac-derived stem/progenitor cells (hCPC) are promising candidates for cardiac repair. They interact with T cells, major effectors of the adaptive immune response, inducing 'paracrine' anti-inflammatory effects that could sustain tissue repair/regeneration. Natural killer (NK) cells are major effectors of the innate immune system that might influence the persistence of therapeutic stem/progenitor cells. Therefore, to get through successful clinical translation and anticipate allogeneic hCPC persistence, we defined their crosstalk with NK cells under steady state and inflammatory conditions.
  
  
  RESULTS
  By using an experimental model of allogeneic hCPC/NK cell interaction, we demonstrate that hCPC moderately trigger cytokine-activated, but not resting, NK cell killing that occurs through formation of lytic immunological synapse and NK cell natural cytotoxicity. Yet, inflammatory context substantially decreases their capacity to set cytokine-activated NK cell functions towards NK cell-cytotoxicity and protects hCPC from NK cell killing. Allogeneic hCPC also restrain NK cell-cytotoxicity against conventional targets and inflammatory cytokine secretion biasing the latter towards anti-inflammatory cytokines. Thus, hCPC are unprivileged targets for allogeneic NK cells and can restrain NK cell functions in allogeneic setting.
  
  
  CONCLUSIONS
  Collectively, our data suggest that allogeneic hCPC/innate NK cells crosstalk within injured inflamed myocardium would permit their retention and might contribute to attenuating inflammation and to preventing adverse cardiac remodelling.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Transplantex, Hôpital Saint Louis, CIB-HOG, AP-HP, Batiment Bazin, 1 Avenue Claude Vellefaux, Paris 75010, France.
authors.forename: Wahid
authors.initials: W
authors.lastname: Boukouaci
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Transplantex, Hôpital Saint Louis, CIB-HOG, AP-HP, Batiment Bazin, 1 Avenue Claude Vellefaux, Paris 75010, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Lauden
authors.affiliation: INSERM UMR 1043 and CNRS UMR 5282, University Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Johan
authors.initials: J
authors.lastname: Siewiera
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Transplantex, Hôpital Saint Louis, CIB-HOG, AP-HP, Batiment Bazin, 1 Avenue Claude Vellefaux, Paris 75010, France Coretherapix S.L., Madrid, Spain.
authors.forename: Noemie
authors.initials: N
authors.lastname: Dam
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Transplantex, Hôpital Saint Louis, CIB-HOG, AP-HP, Batiment Bazin, 1 Avenue Claude Vellefaux, Paris 75010, France.
authors.forename: Hocine-Rachid
authors.initials: HR
authors.lastname: Hocine
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Transplantex, Hôpital Saint Louis, CIB-HOG, AP-HP, Batiment Bazin, 1 Avenue Claude Vellefaux, Paris 75010, France.
authors.forename: Zena
authors.initials: Z
authors.lastname: Khaznadar
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Transplantex, Hôpital Saint Louis, CIB-HOG, AP-HP, Batiment Bazin, 1 Avenue Claude Vellefaux, Paris 75010, France.
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
authors.affiliation: Coretherapix S.L., Madrid, Spain.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Borlado
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Transplantex, Hôpital Saint Louis, CIB-HOG, AP-HP, Batiment Bazin, 1 Avenue Claude Vellefaux, Paris 75010, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.affiliation: INSERM UMR 1043 and CNRS UMR 5282, University Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Nabila
authors.initials: N
authors.lastname: Jabrane-Ferrat
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS940, Institut Universitaire d'Hématologie, Université Paris-Diderot and Laboratoire d'Immunologie et d'Histocompatibilité, Transplantex, Hôpital Saint Louis, CIB-HOG, AP-HP, Batiment Bazin, 1 Avenue Claude Vellefaux, Paris 75010, France reem.al-daccak@inserm.fr.
authors.forename: Reem
authors.initials: R
authors.lastname: Al-Daccak
mesh_terms: D002450:Cell Communication; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D032383:Myocytes, Cardiac / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D011971:Receptors, Immunologic
keywords: Allogenicity; Human cardiac stem/progenitor cells; Myocardial infarction; NK cells