| First Author | Harel M | Year | 2020 |
| Journal | J Immunol | Volume | 205 |
| Issue | 4 | Pages | 1167-1175 |
| PubMed ID | 32651219 | Mgi Jnum | J:294227 |
| Mgi Id | MGI:6455097 | Doi | 10.4049/jimmunol.2000168 |
| Citation | Harel M, et al. (2020) Production of IL-18 Binding Protein by Radiosensitive and Radioresistant Cells in CpG-Induced Macrophage Activation Syndrome. J Immunol 205(4):1167-1175 |
| abstractText | IL-18 binding protein (IL-18BP) acts as a naturally occurring IL-18 decoy receptor. If the balance between IL-18 and IL-18BP is dysregulated, abnormal levels of free bioactive IL-18 are detected, such as in the sera of Il-18bp knockout (KO) mice with CpG-induced macrophage activation syndrome. To determine the cellular sources of Il-18bp in vivo, we selectively depleted Il-18bp expression in either radiosensitive or radioresistant cells using bone marrow transfer between wild-type (WT) and Il-18bp KO mice. Following repeated CpG injections, Il-18bp KO (donor)--> Il-18bp KO (recipient) chimeric mice exhibited more severe disease, with an enhanced Ifn-gamma signature and circulating free Il-18 levels, in comparison with WT-->WT chimeras. Interestingly, the phenotype of KO-->WT and WT-->KO mice did not differ from that of WT-->WT mice. Consistent with this finding, serum Il-18bp levels were similar in these three groups of mice. The contribution of radioresistant and radiosensitive cells to Il-18bp production varied markedly according to the organ examined, with a major contribution of radiosensitive cells in the spleen as opposed to a major contribution of radioresistant cells in the lung. Finally, Ifn-gamma blockade abrogated the CpG-induced but not the constitutive Il-18bp production. Our results demonstrate that circulating Il-18bp is induced in response to Ifn-gamma during CpG-induced macrophage activation syndrome and is present at high levels in the circulation to prevent the deleterious systemic effects of Il-18. |
