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Early IFNβ secretion determines variable downstream IL-12p70 responses upon TLR4 activation in health and disease

Abstract : The IL-12 family of cytokines comprises the only heterodimeric cytokines mediating diverse functional effects. We previously observed a bi-modal IL-12p70 response to LPS in healthy donors of the Milieu Interieur cohort. Herein, we demonstrate that IFNβ expression serves as an upstream determinant of variable IL-12p70 production. Integrative modelling of proteomic, genetic, epigenomic and cellular data confirmed IFNβ as key for regulation of LPS induced IL12A and IL-12p70 variability. The clinical relevance was supported by reduced and variable IL-12p70 responses in individuals infected with the hepatitis C virus (HCV), and findings that IFN-based therapy for HCV is more likely to fail in those patients with dysregulated pre-treatment IL-12p70 responses. In sum, our systems immunology approach has defined a better understanding of IL-12p70 and IFNβ in healthy and infected persons, providing insights into how common genetic and epigenetic variation may impact immune responses to bacterial infection in health and disease.
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Preprints, Working Papers, ...
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03244390
Contributor : Marie-Christine Vougny <>
Submitted on : Tuesday, June 1, 2021 - 11:06:20 AM
Last modification on : Wednesday, June 23, 2021 - 2:18:12 PM
Long-term archiving on: : Thursday, September 2, 2021 - 6:30:04 PM

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2020.12.19.20248132v1.full.pdf
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Celine Posseme, Alba Llibre, Bruno Charbit, Vincent Bondet, Vincent Rouilly, et al.. Early IFNβ secretion determines variable downstream IL-12p70 responses upon TLR4 activation in health and disease. 2021. ⟨pasteur-03244390⟩

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