10.3389/fimmu.2019.00224.s001 Rosa Sottile Rosa Sottile Giorgia Federico Giorgia Federico Cinzia Garofalo Cinzia Garofalo Rossana Tallerico Rossana Tallerico Maria Concetta Faniello Maria Concetta Faniello Barbara Quaresima Barbara Quaresima Costanza Maria Cristiani Costanza Maria Cristiani Maddalena Di Sanzo Maddalena Di Sanzo Gianni Cuda Gianni Cuda Valeria Ventura Valeria Ventura Arnika Kathleen Wagner Arnika Kathleen Wagner Gianluca Contrò Gianluca Contrò Nicola Perrotti Nicola Perrotti Elio Gulletta Elio Gulletta Soldano Ferrone Soldano Ferrone Klas Kärre Klas Kärre Francesco Saverio Costanzo Francesco Saverio Costanzo Francesca Carlomagno Francesca Carlomagno Ennio Carbone Ennio Carbone Image_1_Iron and Ferritin Modulate MHC Class I Expression and NK Cell Recognition.TIFF Frontiers 2019 MHC-I NK cells iron IFNγ STAT1 HLA 2019-02-28 14:22:03 Figure https://frontiersin.figshare.com/articles/figure/Image_1_Iron_and_Ferritin_Modulate_MHC_Class_I_Expression_and_NK_Cell_Recognition_TIFF/7784174 <p>The ability of pathogens to sequester iron from their host cells and proteins affects their virulence. Moreover, iron is required for various innate host defense mechanisms as well as for acquired immune responses. Therefore, intracellular iron concentration may influence the interplay between pathogens and immune system. Here, we investigated whether changes in iron concentrations and intracellular ferritin heavy chain (FTH) abundance may modulate the expression of Major Histocompatibility Complex molecules (MHC), and susceptibility to Natural Killer (NK) cell cytotoxicity. FTH downregulation, either by shRNA transfection or iron chelation, led to MHC surface reduction in primary cancer cells and macrophages. On the contrary, mouse embryonic fibroblasts (MEFs) from NCOA4 null mice accumulated FTH for ferritinophagy impairment and displayed MHC class I cell surface overexpression. Low iron concentration, but not FTH, interfered with IFN-γ receptor signaling, preventing the increase of MHC-class I molecules on the membrane by obstructing STAT1 phosphorylation and nuclear translocation. Finally, iron depletion and FTH downregulation increased the target susceptibility of both primary cancer cells and macrophages to NK cell recognition. In conclusion, the reduction of iron and FTH may influence the expression of MHC class I molecules leading to NK cells activation.</p>