DNA fragmentation factor of small intestinal enterocyte induced by activation of intraepithelial lymphocyte

上皮内淋巴细胞活化诱导的小肠肠上皮细胞DNA碎片因子

• 批准号: 16590132
• 负责人: MATSUTANI Takaji
• 金额: $ 2.24万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590132/
• 关键词: intestinal epithelial cells (IEC); intra-epithelial lymphocyte (IEL); anti-CD3 mAb; DNA fragmentation; DNA repair; γ-H2AX; Rad50; Mrell; TNFα; パーフォリン

When intraepithelial lymphocytes (IELs) were in vivo stimulated by i.p. injected anti-CD3 mAb, DNA double-strand breaks (DSBs) were induced in the villus epithelial cells of the mouse jejunum. Half of epithelial cells detached into the lumen 4h after the stimulation of IELs. Since DNA fragmentation was no longer detected in epithelial cells which persisted in the villi after the anti-CD3 mAb stimulation, it was suggested that fragmented DNA must have been repaired in the nuclei of the enterocyte.To examine the repair mechanism of DNA, the DSB repair proteins were investigated with the immunohistochemical method. The foci formation of γ-H2AX and Rad50 was observed in the nuclei of the cells where DSBs were induced. Consequently, DNA repair in the enterocyte was strongly indicated. Immunostaining of Mrell, one of the DSB repair proteins, was also detected.DSB repair proteins detected in this study were considered to be recruited to DSB sites for DSB repair. Villus enterocyte is a G_0 cell, different from a spermatocyte, a germ cell in meiosis, where repair molecules always exist. Furthermore, appearance of the DNA repair molecules correlated with the kinetic properties of DNA fragmentation. These results altogether indicate that DNA DSB, perse, does not necessarily result in cell death.

在体内用I.P.刺激上皮内淋巴细胞(IEL)。注射抗CD3单抗后，小鼠空肠绒毛上皮细胞发生DNA双链断裂。IEL刺激4h后，一半的上皮细胞脱离管腔。由于在抗CD3单抗刺激后，绒毛上皮细胞中不再检测到DNA断裂，因此推测DNA碎片在肠细胞的细胞核中已被修复。为了探讨DNA的修复机制，用免疫组织化学方法研究了DSB修复蛋白。γ-H_2AX和RAD_(50)在DSB诱导后的细胞核内可见病灶形成。因此，肠道细胞中的DNA修复被强烈地表明。DSB修复蛋白Mrell的免疫染色也被检测到。本研究中检测到的DSB修复蛋白被认为招募到DSB位点进行DSB修复。绒毛肠上皮细胞是一种G_0细胞，不同于精母细胞，精母细胞是处于减数分裂中的生殖细胞，在减数分裂过程中总是存在修复分子。此外，DNA修复分子的出现与DNA断裂的动力学特性有关。这些结果表明，DNA DSB、PERSE并不一定导致细胞死亡。

项目成果

Accumulation of intestinal intraepithelial lymphocytes in association with lack of polymeric immunoglobulin receptor

肠道上皮内淋巴细胞的积累与缺乏聚合免疫球蛋白受体有关

• 发表时间: 2005
• 期刊: European Journal of Immunology 35・4
• 作者: Abe J;Hosokawa H;Sawada Y;Matsumura K;Kobayashi S;Shino Nakamura-Kikuoka;Takaji Matsutani;松谷 隆治;Shino Nakamura-Kikioka;Takaji Matsutani;Takaji Matsutani;Shino Nakamura-Kikuoka S;松谷 隆治;Makoto Asakawa;Ken-ichi Yamazaki
• 通讯作者: Ken-ichi Yamazaki

胸腺選択によるT細胞受容体レパトアとCDR3長の変化

胸腺选择导致 T 细胞受体库和 CDR3 长度的变化

• 发表时间: 2006
• 期刊: リンパ学 (印刷中)
• 作者: Abe J;Hosokawa H;Sawada Y;Matsumura K;Kobayashi S;Shino Nakamura-Kikuoka;Takaji Matsutani;松谷 隆治
• 通讯作者: 松谷 隆治

WBN/Kob-Ht rats spontaneously develop dermatitis under conventional conditions:: Another possible model for atopic dermatitis

• DOI: 10.1538/expanim.54.461
• 发表时间: 2005-10-01
• 期刊: EXPERIMENTAL ANIMALS
• 影响因子: 2.4
• 作者: Asakawa, M;Yoshioka, T;Horikawa, T
• 通讯作者: Horikawa, T

Evidence for existence of oligoclonal tumor-infiltrating lymphocytes and predominant production of T helper 1/T cytotoxic 1 type cytokines in gastric and colorectal tumors.

胃和结直肠肿瘤中存在寡克隆肿瘤浸润淋巴细胞和 T 辅助细胞 1/T 细胞毒性 1 型细胞因子的主要产生的证据。

• 发表时间: 2004
• 期刊: International Journal of Oncology 25・1
• 作者: Yamazaki;K.;Shimada;S.;Kato-Nagoka;N.;Soga;H.;Itoh;T.;Nanno;M.;Kei Yaguchi;Takaji Matsutani
• 通讯作者: Takaji Matsutani

Evidence for existence of oligoclonal tumor-infiltrating lymphocytes and predominant production of T helper1/cytotoxic 1 type cytokines in gastric and colorectal tumors.

胃和结直肠肿瘤中存在寡克隆肿瘤浸润淋巴细胞和主要产生 T 辅助细胞 1/细胞毒性 1 型细胞因子的证据。

• 发表时间: 2004
• 期刊: Int.J.Oncol. 25
• 作者: Matsutani;T.;Shiiba;K.;Yoshioka;T.;Tsuruta;Y.;Suzuki;R.;Ochi;T.;Itoh;T.;Musha;H.;Mizoi;T.;Sasaki;I.
• 通讯作者: I.