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>