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Class I/II hybrid inhibitory oligodeoxynucleotide exerts Th1 and Th2 double immunosuppression.

ABSTRACT: We designed class I/II hybrid inhibitory oligodeoxynucleotides (iODNs), called iSG, and found that the sequence 5'-TTAGGG-3', which has a six-base loop head structure, and a 3'-oligo (dG)3-5 tail sequence are important for potent immunosuppressive activity. Interestingly, splenocytes isolated from ovalbumin (OVA)-immunized mice and treated with iSG3 showed suppression of not only interleukin (IL)-6, IL-12p35, IL-12p40, and interferon (IFN) ? mRNA expression, but also IL-4 and IL-13 mRNA expression. Thus, both Th2 and Th1 immune responses can be strongly suppressed by iODNs in splenocytes from allergen-immunized mice, suggesting usefulness in the treatment of diseases induced by over-active immune activation.

SUBMITTER: Ito Y

PROVIDER: S-EPMC3668506 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Class I/II hybrid inhibitory oligodeoxynucleotide exerts Th1 and Th2 double immunosuppression.

Ito Yusuke Y Shigemori Suguru S Sato Takashi T Shimazu Tomoyuki T Hatano Konomi K Otani Hajime H Kitazawa Haruki H Shimosato Takeshi T

FEBS open bio 20121112

We designed class I/II hybrid inhibitory oligodeoxynucleotides (iODNs), called iSG, and found that the sequence 5'-TTAGGG-3', which has a six-base loop head structure, and a 3'-oligo (dG)3-5 tail sequence are important for potent immunosuppressive activity. Interestingly, splenocytes isolated from ovalbumin (OVA)-immunized mice and treated with iSG3 showed suppression of not only interleukin (IL)-6, IL-12p35, IL-12p40, and interferon (IFN) γ mRNA expression, but also IL-4 and IL-13 mRNA expressi ...[more]

PMID: 23847756

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Project description:Infections by the soil-transmitted threadworm Strongyloides stercoralis affect 30-100 million people worldwide, predominantly in tropic and sub-tropic regions. Here we assessed the T helper cell phenotypes in threadworm-infected patients and experimental murine infections with focus on CD4+ T cells co-expressing markers of Th2 and Th1 differentiation. We show that mice infected with the close relative S. ratti generate strong Th2 responses characterized by the expansion of CD4+ GATA-3+ cells expressing IL-4/-5/-13 in blood, spleen, gut-draining lymph nodes, lung and gut tissue. In addition to conventional Th2 cells, significantly increased frequencies of GATA-3+T-bet+ Th2/1-hybrid cells were detected in all organs and co-expressed Th2- and Th1-cytokines at intermediate levels. Assessing the phenotype of blood-derived CD4+ T cells from South Indian patients infected with S. stercoralis and local uninfected control donors we found that GATA-3 expressing Th2 cells were significantly increased in the patient cohort, coinciding with elevated eosinophil and IgE/IgG4 levels. A fraction of IL-4+CD4+ T cells simultaneously expressed IFN-? hence displaying a Th2/1 hybrid phenotype. In accordance with murine Th2/1 cells, human Th2/1 cells expressed intermediate levels of Th2 cytokines. Contrasting their murine counterparts, human Th2/1 hybrids were marked by high levels of IFN-? and rather low GATA-3 expression. Assessing the effector function of murine Th2/1 cells in vitro we found that Th2/1 cells were qualified for driving the classical activation of macrophages. Furthermore, Th2/1 cells shared innate, cytokine-driven effector functions with Th1 cells. Hence, the key findings of our study are that T helper cells with combined characteristics of Th2 and Th1 cells are integral to immune responses of helminth-infected mice, but also occur in helminth-infected humans and we suggest that Th2/1 cells are poised for the instruction of balanced immune responses during nematode infections.

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Class I/II hybrid inhibitory oligodeoxynucleotide exerts Th1 and Th2 double immunosuppression.

Publications

Class I/II hybrid inhibitory oligodeoxynucleotide exerts Th1 and Th2 double immunosuppression.

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