The investigation of the role of cytokine from derived epithelial cell for activation γδ T cells in mucosal infection

粘膜感染中衍生上皮细胞细胞因子激活γδT细胞的作用研究

• 批准号: 12470473
• 负责人: NOGUCHI Toshihide
• 金额: $ 6.98万
• 依托单位: Aichi-Gakuin University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470473/
• 关键词: Mucosal infection; IL-15; γδT cell; Th1; 上皮系サイトカイン

To know the role of intraepithelial lymphocyte as an etiology of periodontal disease, the mechanism responsible for C57BL/6 as resistance mice and BALB/c as susceptibility mice to oral infection with Listeria monocytogenes were studied by comparing early IL-15 production in intestinal epithelial cells (i-EC).After mice were inoculated p.o. with viable L. monocytogenes, the bacteria in liver, spleen, mesenteric lymph nodes (MLN) and Peyer's patch (PP) were counted on day 1, 3 or 5. C57BL/6 mice were shown higher level of resistance than BALB/c in all organs. To know the difference of these resistance, we investigate kinetics of the intestinal intraepithelial lymphocytes (i-IEL) during oral infection with L.monocytogenes. There were no significant difference in the absolute : nmber and the ratio of i-IEL subpopulations bearing CD8αα and CDαβ or TCRαβ and γδ on day 1, 3 and 5 after oral infection. Thus, these results suggest that oral infection with L.monocytogenes may not affect the subp … More opulation of i-IEL in each mice. Next, we investigate the difference of cytokines production in i-EC and i-IEL after oral infection. High levels of IL-15 mRNA and IL-15 protein in i-EC from C57BL/6 mice were expressed on day 1 after L.monocytogenes infection, whereas in i-EC from BALB/c mice, those were expressed very low. Concurrently, a amount of IFN-γ which was produced by i-IEL from C57BL/6 mice in response to CD3 stimulation were higher than by that from BALB/c mice. While the i-IEL from BALB/c mice produced a higher level of IL-4 upon CD3 stimulation than that of C57BL/6 mice. The toll-like receptor (TLR) 2 has been suggested as a receptor for bacterial lipoproteins from Mycobacteria or Gram-positive bacteria. The mRNA expression level of TLR2, which is recognized to mediate a partly signaling for IL-15 gene transcription, was increased in i-EC from C57BL/6 mice on day 1 after L.monocytogenes infection.These results suggest that TLR2 expression regards difference of IL-15 production, and that the difference in early production of IL-15 by i-EC may at least partly underlie the difference in susceptibility to L.monocytogenes between C57BL/6 and BALB/c mice. Less

为了了解上皮内淋巴细胞作为牙周病病因的作用，通过比较肠上皮细胞（i-EC）中早期IL-15的产生，研究了C57BL/6作为耐药小鼠和BALB/c作为易感小鼠对单核细胞增生李斯特菌口腔感染的机制。使用活的单核细胞增生李斯特氏菌，在第1、3或5天对肝脏、脾脏、肠系膜淋巴结（MLN）和派尔氏淋巴结（PP）中的细菌进行计数。C57BL/6小鼠在所有器官中均表现出比BALB/c更高水平的抵抗力。为了了解这些耐药性的差异，我们研究了单核细胞增生李斯特菌口腔感染期间肠上皮内淋巴细胞 (i-IEL) 的动力学。口腔感染后第1、3、5天携带CD8αα和CDαβ或TCRαβ和γδ的i-IEL亚群的绝对数和比例无显着差异。因此，这些结果表明单核细胞增生李斯特氏菌的口腔感染可能不会影响每只小鼠中 i-IEL 的亚群。接下来，我们研究口腔感染后 i-EC 和 i-IEL 中细胞因子产生的差异。 C57BL/6 小鼠 i-EC 中的 IL-15 mRNA 和 IL-15 蛋白在单核细胞增多性李斯特菌感染后第 1 天表达高水平，而在 BALB/c 小鼠 i-EC 中表达水平非常低。同时，C57BL/6小鼠的i-IEL响应CD3刺激产生的IFN-γ的量高于BALB/c小鼠的IFN-γ量。而 BALB/c 小鼠的 i-IEL 在 CD3 刺激后产生的 IL-4 水平高于 C57BL/6 小鼠。 Toll 样受体 (TLR) 2 被认为是来自分枝杆菌或革兰氏阳性菌的细菌脂蛋白的受体。 TLR2 的 mRNA 表达水平在 C57BL/6 小鼠的 i-EC 中在单核细胞增多性李斯特菌感染后第 1 天增加，TLR2 被认为介导 IL-15 基因转录的部分信号传导。这些结果表明，TLR2 表达与 IL-15 产生的差异有关，并且 i-EC 早期产生 IL-15 的差异可能至少部分是对 L.monocytogenes 的敏感性差异的基础。 C57BL/6 和 BALB/c 小鼠之间的单核细胞增生李斯特氏菌。较少的

项目成果

Mitani A. et al.: "Interleukin-15 production at the early stage after oral infection with Listeria monocytogenes in mice"Immunology. 97(1). 92-99 (1999)

Mitani A. 等人：“小鼠口腔感染单核细胞增生李斯特氏菌后早期白细胞介素 15 的产生”免疫学。

Noguchi T. et al.: "Activation of T cells recognizing an epitope of heat shock protein (HSP)70 can protect against rat adjuvant arthritis"J.Immunol. 163. 5560-5565 (1999)

Noguchi T. 等人：“识别热休克蛋白 (HSP)70 表位的 T 细胞的激活可以预防大鼠佐剂关节炎”J.Immunol。

Noguchi T. et al.: "Activation of T cells recognizing an epitope of heat shock protein (HSP)70 can protect against rat adjuvant arthritis"J. Immunol. 163. 5560-5565 (1999)

Noguchi T. 等人：“激活识别热休克蛋白 (HSP)70 表位的 T 细胞可以预防大鼠佐剂性关节炎”。

Noguchi T. et al.: "Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via toll-like receptors"J. Immunol. 166(5). 3574-3579 (2001)

Noguchi T.等人：“小鼠成骨细胞中脂多糖通过Toll样受体诱导破骨细胞分化因子的基因表达”J.

Noguchi T. et al.: "Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via toll-like receptors"J.Immunol. 166(5). 3574-3579 (2001)

Noguchi T.等人：“小鼠成骨细胞中脂多糖通过Toll样受体诱导破骨细胞分化因子的基因表达”J.Immunol。