Iron and Ferritin Modulate MHC Class I Expression and NK Cell Recognition

Frontiers in Immunology

Francesco Saverio Costanzo¹  Nicola Perrotti²  Gianluca Contrò²  Arnika Kathleen Wagner³  Klas Kärre³  Rosa Sottile³  Ennio Carbone³  Giorgia Federico⁴  Francesca Carlomagno⁴  Soldano Ferrone⁵  Valeria Ventura⁶  Elio Gulletta⁶  Gianni Cuda⁷  Barbara Quaresima⁸  Maddalena Di Sanzo⁸  Maria Concetta Faniello⁸  Cinzia Garofalo⁹  Costanza Maria Cristiani⁹  Rossana Tallerico⁹ 

[1] CIS for Genomics and Molecular Pathology, Magna Graecia University of Catanzaro, Catanzaro, Italy;Department of Health Sciences, University of Catanzaro Magna Graecia, Catanzaro, Italy;Department of Microbiology, Cell and Tumor Biology (MTC), Karolinska Institutet, Stockholm, Sweden;Department of Molecular Medicine and Medical Biotechnologies Federico II University, Naples, Italy;Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States;Division of Clinical Pathology, Department of Health Sciences, Magna Graecia University, Catanzaro, Italy;Laboratory of Proteomics, Research Center of Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Catanzaro, Italy;Research Center of Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Catanzaro, Italy;Tumor Immunology and Immunopathology Laboratory, Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy;

关键词: MHC-I;    NK cells;    iron;    IFNγ;    STAT1;    HLA;   

DOI  :  10.3389/fimmu.2019.00224

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown