| Project/Area Number |
22790480
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
IMANISHI Takayuki 独立行政法人理化学研究所, 免疫シグナル研究グループ, 研究員 (10513442)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | TLR / TCR / 共刺激 / Th1 / Th17 / メモリーT細胞 / IL-2 / エフェクターT細胞 / T細胞 |
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| Research Abstract |
Recent studies including ours have shown that Toll-like receptors(TLRs) are functionally expressed not only on innate immune cells, but also on T cells, and some TLR ligands exhibit costimulatory functions of T cells in response to TCR stimulation to induce cytokine production and cell survival. Particularly, we have shown only TLR2 ligands directly induce IFN-γproduction, cell proliferation, and cell survival without TCR stimulation. In this study, we demonstrated that stimulation with TLR2 ligand promoted Th17 differentiation through the enhanced induction of RORγt expression. This increased Th17 differentiation is associated with an augmented activation of NF-κB and NFAT. And we also demonstrated that stimulation by TLR2 enhanced TCR-mediated IL-17 production and cell proliferation. However, stimulation with TLR2 ligand plus IL-2 or IL-23 did not induce cytokine production such as IL-17 and IL-22 without TCR stimulation, whereas IL-1βinduced IL-22 production in the presence of IL-2 or IL-23.In contrast to Th17 cells, stimulation with TLR2 ligand plus IL-2 robustly induced IL-22 production from Th1 cells. We also found that stimulation with TLR2 ligand plus IL-12 induced IFN-γproduction was impaired in memory phenotype T cells due to down-regulation of TLR2 expression. These findings reveal the cell-type specific differential role of TLR2 in the direct regulation of T cell response.
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