Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome.
Fiche publication
Date publication
septembre 2016
Journal
Journal of immunology (Baltimore, Md. : 1950)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DEVILLIERS Hervé
Tous les auteurs :
Hervier B, Perez M, Allenbach Y, Devilliers H, Cohen F, Uzunhan Y, Ouakrim H, Dorgham K, Méritet JF, Longchampt E, Stenzel W, Cremer I, Benveniste O, Vieillard V
Lien Pubmed
Résumé
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.
Mots clés
Adult, Aged, CD57 Antigens, genetics, Female, Granzymes, Humans, Interferon-gamma, biosynthesis, Interleukin-12, blood, Interleukin-18, blood, K562 Cells, Killer Cells, Natural, immunology, Lung, immunology, Lung Diseases, Interstitial, immunology, Male, Middle Aged, Myositis, immunology, Natural Cytotoxicity Triggering Receptor 3, genetics, Phenotype, Tumor Necrosis Factor-alpha, biosynthesis, Young Adult
Référence
J. Immunol.. 2016 09 1;197(5):1621-30