Departments of Microbiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan.
Immunobiology. 2012 Apr;217(4):446-54. doi: 10.1016/j.imbio.2011.10.009. Epub 2011 Nov 6.
Contact hypersensitivity (CHS) is thought to be associated mainly with the activation of T helper (Th) type 1 cells. However, evidence also suggests that Th type 2 cells (Th2) and cytokines play roles in the development of CHS in humans. The present study examines the Th2 response during the development of CHS in response to 2,4,6-trinitrochlorobenzene (TNCB) in GATA-3-transgenic (GATA-3 Tg) mice. GATA-3 Tg mice were immunized with 7% TNCB applied to abdominal shaved skin. Seven days later, the mice were challenged with 1% TNCB applied to the left ear. Ear swelling, cytokine production in the skin of the ear, and the levels of IgE, IgG1 and IgG2a were measured. Furthermore, we examined the effects of medical treatment on TNCB-induced contact dermatitis using this model. The ear-swelling responses of TNCB-sensitized/challenged GATA-3 Tg mice were significantly greater than those of similarly treated wild-type (WT) mice. The expression of both IL-5 and IL-13 in TNCB sensitized/challenged skin tissues and the IgE response after challenge were obviously increased in the GATA-3 Tg mice, whereas the expression of IFN-γ was identical in the challenged skin tissues of GATA-3-Tg and WT mice. When TNCB-sensitized GATA-3 Tg mice were treated with a high dose of tacrolimus, ear swelling was not significantly decreased, compared with the results in WT mice. These results suggest that GATA-3-induced Th2-dominant responses play a critical role in the pathogenesis of allergic types of dermatitis, such as atopic dermatitis, and may lead to useful new drug development in the future.
接触性超敏反应（CHS）被认为主要与辅助性 T 细胞（Th）1 型细胞的激活有关。然而，有证据表明 Th2 细胞（Th2）和细胞因子在人类 CHS 的发展中也发挥作用。本研究探讨了 GATA-3 转基因（GATA-3 Tg）小鼠在 2,4,6-三硝基氯苯（TNCB）诱导的 CHS 发展过程中的 Th2 反应。GATA-3 Tg 小鼠用 7% TNCB 涂于腹部剃毛皮肤进行免疫。7 天后，用 1% TNCB 涂于左耳进行攻毒。测量耳肿胀、耳部皮肤细胞因子产生、IgE、IgG1 和 IgG2a 水平。此外，我们使用该模型研究了药物治疗对 TNCB 诱导的接触性皮炎的影响。与经同样处理的野生型（WT）小鼠相比，TNCB 致敏/攻毒的 GATA-3 Tg 小鼠的耳肿胀反应显著增强。GATA-3 Tg 小鼠 TNCB 致敏/攻毒皮肤组织中 IL-5 和 IL-13 的表达以及攻毒后的 IgE 反应明显增加，而 GATA-3-Tg 和 WT 小鼠攻毒皮肤组织中 IFN-γ 的表达相同。当 TNCB 致敏的 GATA-3 Tg 小鼠用高剂量他克莫司治疗时，与 WT 小鼠的结果相比，耳肿胀未明显减轻。这些结果表明，GATA-3 诱导的 Th2 优势反应在特应性皮炎等过敏性皮炎的发病机制中起关键作用，并可能为未来的新药开发提供依据。
