BIA, UR1268, INRA, Nantes, France.
UNIV Nantes, Institut du thorax, INSERM CNRS, Nantes, France.
Allergy. 2018 Jul;73(7):1505-1514. doi: 10.1111/all.13386. Epub 2018 Feb 20.
The mechanisms of the atopic march, characterized by a natural progression from food and cutaneous allergies to rhinitis and asthma, are still unknown. However, as several organs can be involved, chemokines and their receptors might be implicated in this process and may be instrumental factors.
We hypothesized that the T-cell gut-homing receptor CCR9 could be implicated in the evolution of allergic diseases.
We characterized the immune response and the role of CCR9 in a murine model combining food allergy to wheat gliadin and a model of acute airways inflammation in response to house dust mite.
Compared with solely asthmatic-like mice, we demonstrated that the aggravation of pulmonary symptoms in consecutive food and respiratory allergies, characterized by an increase in pulmonary resistance and a higher Th17/Treg ratio, was abrogated in CCR9 knockout mice. Moreover, transfer of food-allergic CD4 T cells from wild-type but not from CCR9 aggravated airways inflammation demonstrating that CCR9 is involved in food allergy-enhanced allergic airway inflammation to unrelated allergens.
Taken together, our results demonstrated a crucial role of the T-cell homing receptor CCR9 in this model and validated its potential for use in the development of therapeutic strategies for allergic diseases.
特应性进行曲的机制特征是食物和皮肤过敏自然发展为鼻炎和哮喘，但其机制尚不清楚。然而，由于多个器官可能受到影响，趋化因子及其受体可能参与了这一过程，并且可能是重要的因素。
我们假设 T 细胞归巢受体 CCR9 可能与过敏疾病的演变有关。
我们在一种结合了小麦麦胶蛋白食物过敏和对屋尘螨急性气道炎症反应的小鼠模型中，对免疫反应和 CCR9 的作用进行了表征。
与仅表现为哮喘样的小鼠相比，我们证明了在连续的食物和呼吸道过敏中，肺部症状的加重（表现为肺阻力增加和 Th17/Treg 比值升高）在 CCR9 敲除小鼠中被消除。此外，从野生型而非 CCR9 转移食物过敏的 CD4 T 细胞加重了气道炎症，表明 CCR9 参与了食物过敏增强对无关变应原的过敏性气道炎症。
综上所述，我们的结果表明 T 细胞归巢受体 CCR9 在该模型中具有关键作用，并验证了其在开发过敏疾病治疗策略方面的潜力。
