Imura K, Yoshioka T, Hikita I, Hirasawa T, Sakata T, Matsutani T, Horikawa T, Arimura A
Discovery Research Laboratories, Shionogi and Co. Ltd, Osaka, Japan.
Clin Exp Dermatol. 2009 Jan;34(1):61-7. doi: 10.1111/j.1365-2230.2008.02921.x.
Although dry skin and T cell-dependent disease exacerbation are characteristic features of atopic dermatitis (AD), the involvement of T cells in the development of dry skin remains unclear.
We aimed to elucidate the role of T cells in the development of dry skin in DS-Nh mice as a model for AD, and to evaluate this skin condition pharmacologically.
We prepared DS-Nh mice harbouring a T-cell receptor (TCR)Vbeta(a) haplotype with a central deletion in the TCRBV gene segments, and mice harbouring a TCRVbeta(b) haplotype without any deletion. We analysed the TCRVbeta chain usage and cytokine response to antimouse CD3 monoclonal antibodies in the splenocytes from the two mouse substrains. Transepidermal water loss (TEWL) was measured, and histochemical examination of these mice was carried out. Finally, a pharmacological analysis using loratadine was also performed to evaluate the features of spontaneous dry skin in DS-Nh mice as a model of AD.
Although the deletion of TCRBV gene segments in the TCRVbeta(a) haplotype yielded different representations of each TCRVbeta mRNA, this deletion did not evoke distinct cytokine profiles in the splenocytes compared with those of mice with the TCRVbeta(b) haplotype. Furthermore, our results indicated that the onset of dry skin occurred earlier in mice with TCRVbeta(b) than in those with TCRVbeta(a). Pharmacologically, AD-like dry skin in DS-Nh with TCRVbeta(b) mice is susceptible to an H1 blocker.
A specific lymphocyte subpopulation bearing T-cell receptors may be responsible for loratadine-responsive dermatitis in DS-Nh mice.
尽管皮肤干燥和T细胞依赖性疾病加重是特应性皮炎（AD）的特征性表现，但T细胞在皮肤干燥发生过程中的作用仍不清楚。
我们旨在阐明T细胞在作为AD模型的DS-Nh小鼠皮肤干燥发生过程中的作用，并从药理学角度评估这种皮肤状况。
我们制备了携带T细胞受体（TCR）Vβ(a)单倍型且TCRBV基因片段有中央缺失的DS-Nh小鼠，以及携带无任何缺失的TCRVβ(b)单倍型的小鼠。我们分析了这两个小鼠亚系脾细胞中TCRVβ链的使用情况以及对抗小鼠CD3单克隆抗体的细胞因子反应。测量了经表皮水分流失（TEWL），并对这些小鼠进行了组织化学检查。最后，还使用氯雷他定进行了药理学分析，以评估作为AD模型的DS-Nh小鼠自发性皮肤干燥的特征。
尽管TCRVβ(a)单倍型中TCRBV基因片段的缺失导致每个TCRVβ mRNA有不同的表现形式，但与具有TCRVβ(b)单倍型的小鼠相比，这种缺失并未在脾细胞中引发明显不同的细胞因子谱。此外，我们的结果表明，TCRVβ(b)小鼠的皮肤干燥发病比TCRVβ(a)小鼠更早。从药理学角度来看，具有TCRVβ(b)的DS-Nh小鼠中类似AD的皮肤干燥对H1阻滞剂敏感。
带有T细胞受体的特定淋巴细胞亚群可能是DS-Nh小鼠中对氯雷他定有反应的皮炎的原因。
