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）是T-Helper（Th）1细胞的激活。 -13，STAT6缺陷（STAT6 - / - ）和野生型对照（WT）是接触敏化的5％TNCB，0.5％DNFB或5％OXA，并检查了皮肤反应。在STAT6 - / - 小鼠中，皮肤中的嗜酸性粒细胞和中性粒子与WT小鼠相比，在STAT6 - / - 小鼠中降低了，而TNBS修饰的脾细胞刺激了T细胞的上清液以及IGG1响应后的T细胞。在STAT6/小鼠中，而挑战后Nγ战冰和WT小鼠的表达。帕利斯在CHS的I nDuctlaspase中起关键作用。

项目成果

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Yokozeki, H, Ghoreishi M, Takagaw S. et al: "STAT6 is essential in the induction of contact hypersensitivity"J. Exp. Medicine. in press. (2000)

Yokozeki, H, Ghoreishi M, Takagaw S. 等人：“STAT6 在接触性超敏反应的诱导中至关重要”J.

Takayama K,Yokozeki H et al: "IL-4 inhibits the migration of human Langerhans cells through the downregulation of TNF-receptor II expression"J Invest Dermatol. 113. 541-546 (1999)

Takayama K、Yokozeki H 等人：“IL-4 通过下调 TNF 受体 II 表达来抑制人朗格汉斯细胞的迁移”J Invest Dermatol。

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Yokozeki H 等人：“STAT 6 对于接触性超敏反应的诱导至关重要”J Exp Med。

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