%0 Journal Article %1 noauthororeditor %A et al., Celine Posseme %D 2022 %J Cell Rep. %K TLR4 activation %N 13 %P 110989 %R 10.1016/j.celrep.2022.110989 %T Early IFNβ secretion determines variable downstream IL-12p70 responses upon TLR4 activation %V 39 %X The interleukin-12 (IL-12) family comprises the only heterodimeric cytokines mediating diverse functional effects. We previously reported a striking bimodal IL-12p70 response to lipopolysaccharide (LPS) stimulation in healthy donors. Herein, we demonstrate that interferon β (IFNβ) is a major upstream determinant of IL-12p70 production, which is also associated with numbers and activation of circulating monocytes. Integrative modeling of proteomic, genetic, epigenomic, and cellular data confirms IFNβ as key for LPS-induced IL-12p70 and allowed us to compare the relative effects of each of these parameters on variable cytokine responses. Clinical relevance of our findings is supported by reduced IFNβ-IL-12p70 responses in patients hospitalized with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or chronically infected with hepatitis C (HCV). Importantly, these responses are resolved after viral clearance. Our systems immunology approach defines 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.

@article{noauthororeditor, abstract = {The interleukin-12 (IL-12) family comprises the only heterodimeric cytokines mediating diverse functional effects. We previously reported a striking bimodal IL-12p70 response to lipopolysaccharide (LPS) stimulation in healthy donors. Herein, we demonstrate that interferon β (IFNβ) is a major upstream determinant of IL-12p70 production, which is also associated with numbers and activation of circulating monocytes. Integrative modeling of proteomic, genetic, epigenomic, and cellular data confirms IFNβ as key for LPS-induced IL-12p70 and allowed us to compare the relative effects of each of these parameters on variable cytokine responses. Clinical relevance of our findings is supported by reduced IFNβ-IL-12p70 responses in patients hospitalized with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or chronically infected with hepatitis C (HCV). Importantly, these responses are resolved after viral clearance. Our systems immunology approach defines 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.}, added-at = {2022-09-04T09:48:33.000+0200}, author = {et al., Celine Posseme}, biburl = {https://www.bibsonomy.org/bibtex/27c0e4042b0d7728163b6b4f2e916988a/lkanth}, description = {Early IFNβ secretion determines variable downstream IL-12p70 responses upon TLR4 activation: Cell Reports}, doi = {10.1016/j.celrep.2022.110989}, interhash = {b1555b924efef05816dd11e4a74a3f3f}, intrahash = {7c0e4042b0d7728163b6b4f2e916988a}, journal = {Cell Rep.}, keywords = {TLR4 activation}, month = {Jun 28}, number = 13, pages = 110989, timestamp = {2022-09-04T09:48:33.000+0200}, title = {Early IFNβ secretion determines variable downstream IL-12p70 responses upon TLR4 activation}, volume = 39, year = 2022 }