Analysis of the role of STAT6 signaling in the induction of CHS

STAT6信号在CHS诱导中的作用分析

• 批准号: 10670781
• 负责人: YOKOZEKI Hiroo
• 金额: $ 1.98万
• 依托单位: Tokyo Medical and Dental University, Graduate school
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670781/
• 关键词: STAT6; Th2; Contact Hypersensitivity; Hapten; Cytokine; Langerhans cells; ハプテン; IL-4; IL-13

Contact hypersensitivity (CHS) is thought to be mainly associated with the activation of T-helper (Th) 1 cells. However, there is also evidence that Th2 cells or Th2 cytokines play a role in the development of CHS.In order to analyze the functional contribution of Th2 cvtokines, IL-4 and IL-13, STAT6 deficient (STAT6-/-) and wild-type control (wt) mice (C57BL/6) were contact sensitized with 5% TNCB, 0.5 % DNFB or 5% Oxa, and then any skin reactions were examined. Ear swelling was significantly reduced with a delayed peak response in STAT6-/- mice as compared with wt mice.A histological analysis revealed that the infiltration of both eosinophils and neutrophils in the skin challenged after 24 h in STAT6-/- mice decreasead substantially in comparison with that in wt mice. The expression of Th2 cytokines (IL-4, IL-5 ) in TNCB-challenged skin tissues and the supernatants from T cells stimulated by TNBS -modified spleen cells as well as the IgE and IgG1 response after challenge were also profoundly reduced in STAT6-/- mice, whereas the expression of IFN γ was the same in STAT6-/- mice and wt mice after challenge. Furthermore, Adoptive transfer experiments revealed that STAT6-/- mice induced the contact hypersensitivity after injection of lymph node cells obtained from sensitized wt mice.Our data suggest that the STAT6 signal palys a critical role in the i nductionphase of CHS.

接触性超敏反应(CHS)被认为主要与T辅助细胞(Th)1细胞的激活有关。为了分析Th2细胞因子、IL-4和IL-13的功能作用，对STAT6基因缺陷小鼠(STAT6-/-)和野生型对照小鼠(C57BL/6)分别用5%TNCB、0.5%DNFB和5%Oxa进行接触致敏，然后检测皮肤反应。与Wt小鼠相比，STAT6-/-小鼠的耳肿胀明显减轻，峰值反应延迟。组织学分析显示，与Wt小鼠相比，STAT6-/-小鼠在攻击24小时后，皮肤中嗜酸性粒细胞和中性粒细胞的渗透明显减少。TnCB诱导的小鼠皮肤组织和经TnBS修饰的脾细胞刺激的T细胞培养上清液中Th2型细胞因子(IL-4、IL-5)的表达以及攻击后的免疫球蛋白Ig和Ig_1应答也显著降低，而干扰素γ的表达在TnCB-/-小鼠和Wt小鼠中无明显变化。过继转移实验表明，STAT6-/-小鼠在注射致敏小鼠的淋巴结细胞后发生了接触性超敏反应，提示STAT6信号在CHS的诱导期起着关键作用。

项目成果

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