| First Author | Crisler WJ | Year | 2019 |
| Journal | Life Sci Alliance | Volume | 2 |
| Issue | 5 | PubMed ID | 31585982 |
| Mgi Jnum | J:287460 | Mgi Id | MGI:6391668 |
| Doi | 10.26508/lsa.201900447 | Citation | Crisler WJ, et al. (2019) Ligand-induced IFNGR1 down-regulation calibrates myeloid cell IFNgamma responsiveness. Life Sci Alliance 2(5) |
| abstractText | The type II IFN (IFNgamma) enhances antimicrobial activity yet also drives expression of genes that amplify inflammatory responses. Hence, excessive IFNgamma stimulation can be pathogenic. Here, we describe a previously unappreciated mechanism whereby IFNgamma itself dampens myeloid cell activation. Staining of monocytes from Listeria monocytogenes-infected mice provided evidence of type I IFN-independent reductions in IFNGR1. IFNgamma was subsequently found to reduce surface IFNGR1 on cultured murine myeloid cells and human CD14(+) peripheral blood mononuclear cells. IFNgamma-driven reductions in IFNGR1 were not explained by ligand-induced receptor internalization. Rather, IFNgamma reduced macrophage Ifngr1 transcription by altering chromatin structure at putative Ifngr1 enhancer sites. This is a distinct mechanism from that used by type I IFNs. Ligand-induced reductions in IFNGR1 altered myeloid cell sensitivity to IFNgamma, blunting activation of STAT1 and 3. Our data, thus, reveal a mechanism by which IFNGR1 abundance and myeloid cell sensitivity to IFNgamma can be modulated in the absence of type I IFNs. Multiple mechanisms, thus, exist to calibrate macrophage IFNGR1 abundance, likely permitting the fine tuning of macrophage activation and inflammation. |
