PURPOSE: To determine how CpG, an immunostimulatory sequence, affects experimental allergic conjunctivitis and to determine the mechanisms of its action. METHODS: Experimental allergic conjunctivitis was induced in mice to investigate the suppressive mechanism of CpG treatment. Cytokine profiling, fluorescence-activated cell sorting analyses, and adoptive transfer were used to analyze suppressive mechanisms after CpG treatment. RESULTS: Administration of the CpG oligonucleotide induced significant splenomegaly. Adoptive transfer of the splenocytes isolated from CpG-treated mice was able to confer resistance to allergen-induced inflammatory responses in recipient mice. CpG treatment led to a transient upregulation of IL-1ra, IL-18, IL-1alpha, and IL-12 in the spleen, draining lymph nodes, and conjunctiva. In contrast, IL-10 showed a marked and sustained induction in the inductive and effector tissues. Splenomegaly after CpG exposure was reduced in IL-10-deficient mice, indicating that IL-10 is required for immune remodeling of the spleen. Analyses of allergen-sensitized mice deficient in IL-10 exacerbated the late-phase inflammatory responses. Fluorescence-activated cell sorting analysis of the CpG-induced splenocyte subsets showed that the predominant source of IL-10 was B220(+) CD19(+) CD23(+)IgM(+)CD40(+)class II(high) follicular B cells. Adoptive transfer of IL-10-deficient B cells exacerbated eosinophilia. Transfer of an expanded population of cells after CpG treatment, including IL-10-secreting follicular B cells, protected against eosinophilia. CONCLUSIONS: CpG treatment provided B cell-mediated regulation of immune responses and B cell differentiation in CpG-induced immune remodeling with the use of IL-10.
PURPOSE: To determine how CpG, an immunostimulatory sequence, affects experimental allergic conjunctivitis and to determine the mechanisms of its action. METHODS: Experimental allergic conjunctivitis was induced in mice to investigate the suppressive mechanism of CpG treatment. Cytokine profiling, fluorescence-activated cell sorting analyses, and adoptive transfer were used to analyze suppressive mechanisms after CpG treatment. RESULTS: Administration of the CpG oligonucleotide induced significant splenomegaly. Adoptive transfer of the splenocytes isolated from CpG-treated mice was able to confer resistance to allergen-induced inflammatory responses in recipient mice. CpG treatment led to a transient upregulation of IL-1ra, IL-18, IL-1alpha, and IL-12 in the spleen, draining lymph nodes, and conjunctiva. In contrast, IL-10 showed a marked and sustained induction in the inductive and effector tissues. Splenomegaly after CpG exposure was reduced in IL-10-deficient mice, indicating that IL-10 is required for immune remodeling of the spleen. Analyses of allergen-sensitized mice deficient in IL-10 exacerbated the late-phase inflammatory responses. Fluorescence-activated cell sorting analysis of the CpG-induced splenocyte subsets showed that the predominant source of IL-10 was B220(+) CD19(+) CD23(+)IgM(+)CD40(+)class II(high) follicular B cells. Adoptive transfer of IL-10-deficient B cells exacerbated eosinophilia. Transfer of an expanded population of cells after CpG treatment, including IL-10-secreting follicular B cells, protected against eosinophilia. CONCLUSIONS: CpG treatment provided B cell-mediated regulation of immune responses and B cell differentiation in CpG-induced immune remodeling with the use of IL-10.
Authors: Hamid Hosseini; Li Yi; Peter Kanellakis; Anh Cao; Christopher Tay; Karlheinz Peter; Alex Bobik; Ban-Hock Toh; Tin Kyaw Journal: J Am Heart Assoc Date: 2018-06-23 Impact factor: 5.501