IL-38 prevents induction of trained immunity by inhibition of mTOR signaling.
J Leukoc Biol
; 110(5): 907-915, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-33620105
ABSTRACT
Trained immunity is the acquisition of a hyperresponsive phenotype by innate immune cells (such as monocytes and macrophages) after an infection or vaccination, a de facto nonspecific memory dependent on epigenetic and metabolic reprogramming of these cells. We have recently shown that induction of trained immunity is dependent on IL-1ß. Here, we show that recombinant IL-38, an anti-inflammatory cytokine of the IL-1-family, was able to induce long-term inhibitory changes and reduce the induction of trained immunity by ß-glucan in vivo in C57BL/6 mice and ex vivo in their bone marrow cells. IL-38 blocked mTOR signaling and prevented the epigenetic and metabolic changes induced by ß-glucan. In healthy subjects, the IL1F10 associated single nucleotide polymorphism rs58965312 correlated with higher plasma IL-38 concentrations and reduced induction of trained immunity by ß-glucan ex vivo. These results indicate that IL-38 induces long-term anti-inflammatory changes and also inhibits the induction of trained immunity. Recombinant IL-38 could therefore potentially be used as a therapeutic intervention for diseases characterized by exacerbated trained immunity.
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Base de dados:
MEDLINE
Assunto principal:
Interleucinas
/
Serina-Treonina Quinases TOR
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Memória Imunológica
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article