| Budget Amount *help |
¥44,200,000 (Direct Cost: ¥34,000,000、Indirect Cost: ¥10,200,000)
Fiscal Year 2020: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2018: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
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| Outline of Final Research Achievements |
Small intestinal mononuclear cells expressing CX3CR1 (CX3CR1+ cells) uptake luminal antigens by protruding their dendrites into the lumen. Mice lacking GPR31, which was highly and selectively expressed in intestinal CX3CR1+ cells, showed defective dendrite protrusions of CX3CR1+ cells in the small intestine. We purified a GPR31-activating fraction of intestinal content. Both lactic acid and pyruvic acid induced dendrite extension of CX3CR1+ cells of wild-type mice, but not GPR31-deficient mice. Oral administration of lactate/pyruvate enhanced dendrite protrusion of CX3CR1+ cells in the intestine of wild-type mice, but not GPR31-deficient mice. Lactate/pyruvate-treated wild-type mice showed enhanced immune response and high resistance to intestinal Salmonella infection. Thus, lactate/pyruvate, which are produced in the intestinal lumen in a bacteria-dependent manner, contribute to enhanced immune responses by inducing GPR31-mediated dendrite protrusion of intestinal CX3CR1+ cells.
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