背景:特应性皮炎(AD)是一种慢性复发性炎症性皮肤病。尽管小鼠研究已经证明2型先天淋巴样细胞(ILC)介导2型皮肤炎症,它们在AD皮肤纤维化中的作用尚不清楚.该研究使用AD样鼠模型调查了2型ILC是否参与皮肤纤维化。
方法:C57BL/6小鼠用烟曲霉(Af)皮下处理,每周连续5天,持续5周,以诱导皮肤纤维化。成熟的淋巴细胞缺陷Rag1-/-小鼠也用于研究2型ILC在皮肤纤维化中的作用。
结果:AD组的临床评分和经表皮失水(TEWL)明显高于对照组。AD组还显示表皮和真皮厚度显著增加,嗜酸性粒细胞数量显著增加,中性粒细胞,肥大细胞,而皮损组的淋巴细胞高于对照组。AD组的病变皮肤显示胶原蛋白染色增加,胶原蛋白水平明显高于对照组(10.4±2.2µg/mgvs.1.6±0.1微克/毫克,P<0.05)。与对照组相比,AD组病灶皮肤中2型ILC的数量显着增加(0.08±0.01%vs.0.03±0.01%,P<0.05)。与它们的对照组相比,这些发现对于Rag1-/-小鼠的AD组也是相似的。使用抗CD90.2单克隆抗体清除2型ILC可显着改善临床症状评分,TEWL,和炎症细胞的浸润,在Rag1-/-小鼠的AD组中观察到胶原蛋白水平显着降低(1.6±0.0μg/mgvs.4.5±0.3μg/mg,P<0.001)。
结论:在Af诱导的AD样小鼠模型中,2型ILC升高,胶原蛋白水平增加。此外,2型ILC的去除导致胶原水平降低和AD样病理结果改善.这些发现表明,2型ILC在AD的皮肤纤维化机制中起作用。
BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease. Although murine studies have demonstrated that type 2 innate lymphoid cells (ILCs) mediate type 2 skin inflammation, their role in skin fibrosis in AD remains unclear. This study investigated whether type 2 ILCs are involved in skin fibrosis using an AD-like murine model.
METHODS: C57BL/6 mice were treated epicutaneously with Aspergillus fumigatus (Af) for 5 consecutive days per week for 5 weeks to induce skin fibrosis. Mature lymphocyte deficient Rag1-/- mice were also used to investigate the role of type 2 ILCs in skin fibrosis.
RESULTS: The clinical score and transepidermal water loss (TEWL) were significantly higher in the AD group than in the control group. The AD group also showed significantly increased epidermal and dermal thicknesses and significantly higher numbers of eosinophils, neutrophils, mast cells, and lymphocytes in the lesional skin than the control group. The lesional skin of the AD group showed increased stain of collagen and significantly higher levels of collagen than the control group (10.4 ± 2.2 µg/mg vs. 1.6 ± 0.1 µg/mg, P < 0.05). The AD group showed significantly higher populations of type 2 ILCs in the lesional skin compared to the control group (0.08 ± 0.01% vs. 0.03 ± 0.01%, P < 0.05). These findings were also similar with the AD group of Rag1-/- mice compared to their control group. Depletion of type 2 ILCs with anti-CD90.2 monoclonal antibodies significantly improved clinical symptom score, TEWL, and infiltration of inflammatory cells, and significantly decreased levels of collagen were observed in the AD group of Rag1-/- mice (1.6 ± 0.0 μg/mg vs. 4.5 ± 0.3 μg/mg, P < 0.001).
CONCLUSIONS: In the Af-induced AD-like murine model, type 2 ILCs were elevated, with increased levels of collagen. Additionally, removal of type 2 ILCs resulted in decreased collagen levels and improved AD-like pathological findings. These findings suggest that type 2 ILCs play a role in the mechanism of skin fibrosis in AD.