嗜酸性粒细胞在MC903诱导小鼠特应性皮炎中的作用及机制初探

The Role and Mechanism of Eosinophils in MC903-induced Atopic Dermatitis in Mice

目的探讨嗜酸性粒细胞(eosinophils,EOS)在特应性皮炎(atopic dermatitis,AD)发病中的作用和潜在机制。方法 MC903(2nmol/L)局部外用于BALB/c(WT)和Δdbl-GATA小鼠耳背,观察临床表现、皮炎评分和病理学表现,并检测血清总IgE、细胞因子及脾脏辅助T细胞亚群的变化。结果 MC903成功诱导WT小鼠和Δdbl-GATA小鼠特应性皮炎样损害。10天后两组在症状程度和皮炎分数上差异无统计学意义(10. 40±0. 56 vs. 10. 86±0. 23,P> 0. 05),但7天时WT组较ΔdblGATA相比,红斑肿胀出现延迟(4. 18±0. 40 vs. 7. 46±0. 52,P <0. 01)。组织病理学检测均表现为表皮增生和真皮内炎症细胞浸润,WT组可见嗜酸性粒细胞。血清总IgE在两组小鼠都升高,WT组升高更显著。WT组小鼠血清中TSLP、IL-6和IL-13均显著升高,IL-17A降低;Δdbl-GATA组TSLP、IL-6、IL-13和IL-17A均较前升高。WT组Th1细胞比例明显降低,Th17比例明显降低,Treg细胞升高;ΔdblGATA组Th1细胞比例较前无明显改变,Th17细胞比例显著升高,Treg细胞比例降低; Th2细胞在两组均无明显变化。结论 EOS在AD发生中发挥了一定的调节作用,EOS可能通过调节Th1、Th17和Treg介导疾病的发展。

Objective To elucidate the role and mechanism underlying the eosinophils( EOS) in the pathogenesis of atopic dermatitis( AD). Methods MC903( 2 nmol/L) was topically applied to dorsal side of left ear once a day for 10 days in both group( WT group and Δdbl-GATA group). Clinical manifestations,dermatitis scores and pathological findings were observed,and changes in serum total IgE,cytokines,and spleen-assisted T cell subsets were determined. Results MC903 successfully induced atopic dermatitis-like lesions in WT mice and Δdbl-GATA mice. There was no significant difference in symptom severity and dermatitis score between the two groups after 10 days( 10. 40 ± 0. 56 vs. 10. 86 ± 0. 23,P > 0. 05). Nonetheless,there was a delay in erythema swelling in the WT group at 7 days compared with Δdbl-GATA group( 4. 18 ±0. 40 vs. 7. 46 ± 0. 52,P < 0. 01). Histopathological examination showed epidermalhyperplasia and inflammatory cells infiltration in dermis in both groups,and eosinophils,in particular,could be seen in WT group. MC903 induced high level of serum total Ig E in both groups; however,the level was much higher in the WT group. Serum TSLP,IL-6 and IL-13 were remarkably increased and IL-17 A was decreased in WT group. In contrast,the cytokines above in Δdbl-GATA group were increased than before. Flow cytometric analysis revealed decreased frequency of Th1,Th17 and increased Treg cells in WT group. In Δdbl-GATA group,the frequency of Th17 increased and a concurrently decreased Treg cells were observed. The Th2 cells in both group were not changed. Conclusion Our results demonstrate EOS plays a regulatory role in the development of AD,specifically mediating the development of the disease by regulating the balance of Th1,Th17 and Treg cells.