Systemic administration of TLR3 agonist induces IL-7 expression and IL-7-dependent CXCR3 ligand production in the lung

Journal of Leukocyte Biology

Jun-O Jin¹  Qing Yu¹ 

[1] Department of Immunology and Infectious Disease, The Forsyth Institute, Cambridge, Massachusetts, USADepartment of Immunology and Infectious Disease, The Forsyth Institute, Cambridge, Massachusetts, USADepartment of Immunology and Infectious Disease, The Forsyth Institute, Cambridge, Massachusetts, USA

关键词: poly I:C;    IFN-γ;    M1 macrophage;    chemokine;    effector T cells;    NK cells;   

DOI  :  10.1189/jlb.0712360

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown