title: Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome.
abstract: Antisynthetase syndrome (aSS) is characterized by the association of interstitial lung disease and myositis with anti-tRNA synthetase autoantibodies. Immune mechanisms leading to aSS could be initiated in the lungs, but the role of NK cells has not yet been studied. Both extensive NK cell phenotype and functions were compared between 33 patients and 26 controls. Direct and redirected polyfunctionality assays (degranulation and intracellular production of TNF-α and IFN-γ) were performed spontaneously or after IL-12 plus IL-18 stimulation in the presence of K562 or P815 target cells, respectively. NK cells from inactive patients showed normal phenotype, whereas active aSS revealed a differentiated NK cell profile, as indicated by increased CD57 and Ig-like transcript 2 and an inability to produce IFN-γ (p = 0.002) compared with controls. Importantly, active aSS was more specifically associated with a significant NKp30 decrease (p = 0.009), although levels of mRNA and intracellular protein were similar in aSS and healthy controls. This NKp30 decrease was strongly correlated with reduced NK cell polyfunctionality in both direct and redirected killing assays with anti-NKp30 Abs (p = 0.009 and p = 0.03, respectively), confirming its important impact in aSS. Histological studies revealed massive infiltrations of NK cells inside the lungs of aSS patients (148 versus 11/mm(2)). Taken together, these data suggest that NK cells and NKp30 could play a role in aSS pathogenesis.
authors: Sorbonne Universités, Université Pierre et Marie Curie Université Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses, 75013 Paris, France; Département de Médecine Interne et Immunologie Clinique, Centre National de Référence des Maladies Musculaires, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, DHU I2B, 75013 Paris, France; INSERM UMR S974, Université Pierre et Marie Curie, 75013 Paris, France; baptiste.hervier@psl.aphp.fr.
authors: Baptiste
authors: 0000-0002-1388-1121
authors: B
authors: Hervier
authors: INSERM UMR S1138, Université Pierre et Marie Curie, Centre de Recherche des Cordeliers, 75006 Paris, France;
authors: Mikaël
authors: 0000-0002-0607-5519
authors: M
authors: Perez
authors: Département de Médecine Interne et Immunologie Clinique, Centre National de Référence des Maladies Musculaires, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, DHU I2B, 75013 Paris, France; INSERM UMR S974, Université Pierre et Marie Curie, 75013 Paris, France; Département de Neuropathologie, Charité-Universitätsmedizin, 10117 Berlin, Germany;
authors: Yves
authors: Y
authors: Allenbach
authors: Département de Médecine Interne et Maladies Systémiques, Hôpital du Bocage, Centre Hospitalier Universitaire, 21000 Dijon, France; INSERM Centre d'Investigation Clinique-Epidémiologie Clinique 1432, 2100 Dijon, France;
authors: Hervé
authors: H
authors: Devilliers
authors: Service de Médecine Interne 2, Centre National de Référence des Maladies Auto-immune et Systémiques Rares, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 75013 Paris, France;
authors: Fleur
authors: F
authors: Cohen
authors: Université Paris 13, Sorbonne Paris Cité, EA 2363, Départment de Pneumologie, Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, 93000 Bobigny, France;
authors: Yurdagül
authors: Y
authors: Uzunhan
authors: INSERM UMR S1138, Université Pierre et Marie Curie, Centre de Recherche des Cordeliers, 75006 Paris, France; Département d'Anatomopathologie, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin-La Roche Guyon, 75014 Paris, France;
authors: Hanane
authors: 0000-0003-3262-8647
authors: H
authors: Ouakrim
authors: Sorbonne Universités, Université Pierre et Marie Curie Université Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses, 75013 Paris, France;
authors: Karim
authors: 0000-0001-9539-3203
authors: K
authors: Dorgham
authors: Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin-La Roche Guyon, 75014 Paris, France; and.
authors: Jean-François
authors: 0000-0002-8942-6977
authors: JF
authors: Méritet
authors: Département d'Anatomopathologie, Hôpital Foch, 92073 Suresnes, France.
authors: Elisabeth
authors: E
authors: Longchampt
authors: Département de Neuropathologie, Charité-Universitätsmedizin, 10117 Berlin, Germany;
authors: Werner
authors: W
authors: Stenzel
authors: INSERM UMR S1138, Université Pierre et Marie Curie, Centre de Recherche des Cordeliers, 75006 Paris, France;
authors: Isabelle
authors: I
authors: Cremer
authors: Département de Médecine Interne et Immunologie Clinique, Centre National de Référence des Maladies Musculaires, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, DHU I2B, 75013 Paris, France; INSERM UMR S974, Université Pierre et Marie Curie, 75013 Paris, France;
authors: Olivier
authors: O
authors: Benveniste
authors: Sorbonne Universités, Université Pierre et Marie Curie Université Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses, 75013 Paris, France;
authors: Vincent
authors: V
authors: Vieillard
mesh_terms: D000328:Adult; D000368:Aged; D018959:CD57 Antigens / Q000235:genetics; D005260:Female; D053804:Granzymes; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000097:blood / Q000276:immunology; D020382:Interleukin-18 / Q000097:blood / Q000276:immunology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009220:Myositis / Q000276:immunology* / Q000503:physiopathology; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D055815:Young Adult
chemical_list: D018959:CD57 Antigens; D020382:Interleukin-18; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D053804:Granzymes