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Production of IL-18 Binding Protein by Radiosensitive and Radioresistant Cells in CpG-Induced Macrophage Activation Syndrome

Published in The Journal of immunology. 2020, vol. 205, no. 4, p. 1167-1175
Abstract 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-γ 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-γ 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-γ during CpG-induced macrophage activation syndrome and is present at high levels in the circulation to prevent the deleterious systemic effects of Il-18.
PMID: 32651219
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Research groups Biologie des cytokines de la famille de l'interleukine-1 (1022)
Mécanisme de l'inflammation articulaire (44)
Swiss National Science Foundation: 310030_712674
Autre: Institute of Rheumatology Research, and the Rheumasearch Foundation
(ISO format)
HAREL, Mathilde Alexia Rolande et al. Production of IL-18 Binding Protein by Radiosensitive and Radioresistant Cells in CpG-Induced Macrophage Activation Syndrome. In: Journal of Immunology, 2020, vol. 205, n° 4, p. 1167-1175. doi: 10.4049/jimmunol.2000168 https://archive-ouverte.unige.ch/unige:144610

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Deposited on : 2020-11-11

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