{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jin JO"],"funding":["NIDCR NIH HHS"],"pagination":["413-25"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4050520"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["93(3)"],"pubmed_abstract":["In this study, we tested the hypothesis that systemic administration of TLR3 agonist poly I:C can enhance T cell infiltration of lung through up-regulating IL-7 expression. poly I:C, a synthetic analog of viral dsRNA and a TLR3 agonist, is studied extensively as vaccine adjuvant as a result of its pleotropic immune-stimulatory effects. Here, we show that systemic poly I:C administration induces substantial IL-7 production in the lung in a type 1 IFN- and IFN-γ-dependent fashion. Blockade of the IL-7Rα signal with a neutralizing antibody abrogated poly I:C-induced MCP-1 up-regulation, macrophage recruitment, and CXCR3 ligand expression in the lung. Conversely, administration of IL-7 enhances these events, and it does so by enhancing T cell IFN-γ production. We also show that the initial up-regulation of CXCR3 ligands and infiltration of T cells in the lung are mediated by poly I:C-induced IFN-γ from NK cells; however, the sustained and optimal CXCR3 ligand expression and T cell infiltration require poly I:C-induced IL-7 and T cell-derived IFN-γ. In a model of multiorgan inflammation elicited by adoptive transfer of immune cells into RAG1(-/-) mice, we show that poly I:C enhances IL-7 production in the lung and promotes expression of CXCR3 ligands and recruitment of IFN-γ(+) T cells in an IL-7-dependent fashion. Collectively, these results strongly support our hypothesis and delineate a new mechanism by which poly I:C boosts the T cell immune response in the lung by inducing local IL-7 production, which in turn, enhances T cell-derived IFN-γ to promote macrophage recruitment, CXCR3 ligand expression, and T cell infiltration."],"journal":["Journal of leukocyte biology"],"pubmed_title":["Systemic administration of TLR3 agonist induces IL-7 expression and IL-7-dependent CXCR3 ligand production in the lung."],"pmcid":["PMC4050520"],"funding_grant_id":["P30DE020751","P30 DE020751"],"pubmed_authors":["Jin JO","Yu Q"],"additional_accession":[]},"is_claimable":false,"name":"Systemic administration of TLR3 agonist induces IL-7 expression and IL-7-dependent CXCR3 ligand production in the lung.","description":"In this study, we tested the hypothesis that systemic administration of TLR3 agonist poly I:C can enhance T cell infiltration of lung through up-regulating IL-7 expression. poly I:C, a synthetic analog of viral dsRNA and a TLR3 agonist, is studied extensively as vaccine adjuvant as a result of its pleotropic immune-stimulatory effects. Here, we show that systemic poly I:C administration induces substantial IL-7 production in the lung in a type 1 IFN- and IFN-γ-dependent fashion. Blockade of the IL-7Rα signal with a neutralizing antibody abrogated poly I:C-induced MCP-1 up-regulation, macrophage recruitment, and CXCR3 ligand expression in the lung. Conversely, administration of IL-7 enhances these events, and it does so by enhancing T cell IFN-γ production. We also show that the initial up-regulation of CXCR3 ligands and infiltration of T cells in the lung are mediated by poly I:C-induced IFN-γ from NK cells; however, the sustained and optimal CXCR3 ligand expression and T cell infiltration require poly I:C-induced IL-7 and T cell-derived IFN-γ. In a model of multiorgan inflammation elicited by adoptive transfer of immune cells into RAG1(-/-) mice, we show that poly I:C enhances IL-7 production in the lung and promotes expression of CXCR3 ligands and recruitment of IFN-γ(+) T cells in an IL-7-dependent fashion. Collectively, these results strongly support our hypothesis and delineate a new mechanism by which poly I:C boosts the T cell immune response in the lung by inducing local IL-7 production, which in turn, enhances T cell-derived IFN-γ to promote macrophage recruitment, CXCR3 ligand expression, and T cell infiltration.","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013 Mar","modification":"2025-04-26T09:50:44.934Z","creation":"2019-03-27T01:29:46Z"},"accession":"S-EPMC4050520","cross_references":{"pubmed":["23271706"],"doi":["10.1189/jlb.0712360"]}}