The present study investigated the role of CD226 in a 2,4-dinitrochlorobenzene (DNCB)-induced mouse model of atopic dermatitis (AD). The results showed that the lack of CD226 (global and CD4 T cell-specific) significantly increased ear thickness, reddening, swelling, and scaling of the skin, as well as inflammatory cell and mast cell infiltration. qPCR results demonstrated that the mRNA expressions of AD-related inflammatory cytokines and chemokines were markedly increased in the draining lymph nodes (dLNs) and lesion ear skin tissues of global and CD4 T cell-specific CD226-deficient mice compared with that in control mice. In vitro assessment revealed that CD226 directly modulates TGF-β-mediated regulatory T (Treg) cell differentiation and proliferation. Notably, Treg cell-specific deletion of CD226 (Cd226Foxp3 mice) resulted in more severe dermatitis and epidermal thickening compared with those observed in littermate mice upon DNCB treatment. Subsequent analysis showed that the infiltration of Treg cells in ear lesions and the number of Tregs in the spleen were significantly reduced in Cd226Foxp3 mice following DNCB treatment. In addition, the lack of CD226 induced apoptosis of Treg cells through the activation of Caspase3. Therefore, these results suggest that CD226 has potential efficacy in AD, correlating with Treg cell inhibition.

中文翻译：

---

共刺激分子 CD226 调节小鼠模型中的特应性皮炎

本研究调查了 CD226 在 2,4-二硝基氯苯 (DNCB) 诱导的特应性皮炎 (AD) 小鼠模型中的作用。结果表明，CD226（整体和 CD4 T 细胞特异性）的缺乏显着增加了耳朵厚度、皮肤发红、肿胀和鳞屑，以及炎症细胞和肥大细胞浸润。qPCR结果表明，与对照小鼠相比，整体和CD4 T细胞特异性CD226缺陷小鼠的引流淋巴结（dLN）和病变耳部皮肤组织中AD相关炎症细胞因子和趋化因子的mRNA表达显着增加。体外评估显示 CD226 直接调节 TGF-β 介导的调节性 T (Treg) 细胞分化和增殖。值得注意的是，与 DNCB 治疗后同窝小鼠中观察到的情况相比，CD226 的 Treg 细胞特异性缺失（Cd226Foxp3 小鼠）导致更严重的皮炎和表皮增厚。随后的分析表明，接受 DNCB 治疗后，Cd226Foxp3 小鼠耳部病变中 Treg 细胞的浸润和脾脏中 Treg 细胞的数量显着减少。此外，CD226的缺乏通过激活Caspase3诱导Treg细胞凋亡。因此，这些结果表明 CD226 在 AD 中具有潜在功效，与 Treg 细胞抑制相关。