Dahten Anja, Koch Christin, Ernst Dennis, Schnöller Corinna, Hartmann Susanne, Worm Margitta
Department of Dermatology and Allergy, Allergy-Center-Charité Campus Mitte Universitätsmedizin Berlin, Berlin, Germany.
J Invest Dermatol. 2008 Sep;128(9):2211-8. doi: 10.1038/jid.2008.84. Epub 2008 Apr 10.
We have shown previously that specific ligands of the peroxisome proliferator-activated receptor-gamma (PPARgamma) inhibit the systemic allergic immune response. The objective of this study was to investigate the impact of PPARgamma-ligand treatment on the local allergic immune response. We established a murine model exhibiting clinical and histological features of AD-like skin lesions with high reproducibility. In this model, the PPARgamma ligand was applied in an either preventive or therapeutic manner via systemic and local routes. The affected skin areas were assessed by standardized skin score, histological analyses, and immunohistochemical examinations. Our data show that systemic application of PPARgamma ligand by a preventive protocol led to significantly reduced onset of eczematous skin lesions. This was confirmed by histology, showing decreased skin thickness accompanied by significantly reduced infiltrations of CD4+ and CD8+ lymphocytes but also mast cells. Additionally, early allergen-specific IgE and IgG1 responses were reduced (day 21/35), whereas IgG2a levels remained unchanged. In conclusion, our results demonstrate that PPARgamma-ligand treatment inhibits not only systemic allergic immune response, but also local allergen-mediated dermatitis. Our findings point to therapeutic strategies, including a PPARgamma-ligand-based treatment.
我们之前已经表明，过氧化物酶体增殖物激活受体γ（PPARγ）的特异性配体可抑制全身性过敏免疫反应。本研究的目的是调查PPARγ配体治疗对局部过敏免疫反应的影响。我们建立了一种具有高度可重复性的、表现出类特应性皮炎皮肤损伤临床和组织学特征的小鼠模型。在该模型中，通过全身和局部途径以预防或治疗方式应用PPARγ配体。通过标准化皮肤评分、组织学分析和免疫组织化学检查对受影响的皮肤区域进行评估。我们的数据表明，通过预防方案全身应用PPARγ配体可显著减少湿疹性皮肤损伤的发作。组织学证实了这一点，显示皮肤厚度降低，同时CD4 +和CD8 +淋巴细胞以及肥大细胞的浸润显著减少。此外，早期过敏原特异性IgE和IgG1反应降低（第21/35天），而IgG2a水平保持不变。总之，我们的结果表明，PPARγ配体治疗不仅抑制全身性过敏免疫反应，而且还抑制局部过敏原介导的皮炎。我们的研究结果指出了治疗策略，包括基于PPARγ配体的治疗。
