Johannesson Bjarki, Sattler Susanne, Semenova Ekaterina, Pastore Saveria, Kennedy-Lydon Teresa M, Sampson Robert D, Schneider Michael D, Rosenthal Nadia, Bilbao Daniel
Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo, 00015, Italy.
National Heart and Lung Institute, Imperial College, London W12 0NN, UK.
Dis Model Mech. 2014 Aug;7(8):977-85. doi: 10.1242/dmm.015362.
Allergic contact dermatitis (ACD) is triggered by an aberrant hyperinflammatory immune response to innocuous chemical compounds and ranks as the world's most prevalent occupational skin condition. Although a variety of immune effector cells are activated during ACD, regulatory T (Treg) cells are crucial in controlling the resulting inflammation. Insulin-like growth factor-1 (IGF-1) regulates cell proliferation and differentiation and accelerates wound healing and regeneration in several organs including the skin. Recently IGF-1 has also been implicated in protection from autoimmune inflammation by expansion of Treg cells. Here, we demonstrate that ectopic expression of IGF-1 in mouse skin suppresses ACD in a Treg cell-specific manner, increasing the number of Foxp3+ Treg cells in the affected area and stimulating lymphocyte production of the anti-inflammatory cytokine interleukin 10. Similar therapeutic effects can be achieved with systemic or topical delivery of IGF-1, implicating this growth factor as a promising new therapeutic option for the treatment of ACD.
过敏性接触性皮炎(ACD)是由对无害化合物的异常高炎症免疫反应引发的,是世界上最常见的职业性皮肤病。虽然在ACD过程中多种免疫效应细胞被激活,但调节性T(Treg)细胞对控制由此产生的炎症至关重要。胰岛素样生长因子-1(IGF-1)调节细胞增殖和分化,并加速包括皮肤在内的多个器官的伤口愈合和再生。最近,IGF-1还被认为通过Treg细胞的扩增来预防自身免疫炎症。在这里,我们证明IGF-1在小鼠皮肤中的异位表达以Treg细胞特异性方式抑制ACD,增加受影响区域中Foxp3 + Treg细胞的数量,并刺激抗炎细胞因子白细胞介素10的淋巴细胞产生。通过全身或局部递送IGF-1可以实现类似的治疗效果,这表明这种生长因子是治疗ACD的一种有前途的新治疗选择。