Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen.
Allergy. 2015 Aug;70(8):921-32. doi: 10.1111/all.12631. Epub 2015 May 15.
IL-35, a new member of the IL-12 family, is an inhibitory cytokine produced by regulatory T and B lymphocytes that play a suppressive role in the inflammatory diseases. This study focuses on the cellular mechanism regulating the anti-inflammatory activity of IL-35 in asthmatic mice.
Ovalbumin-induced asthmatic and humanized asthmatic mice were adopted to evaluate the in vivo anti-inflammatory activities of IL-35. For monitoring the airway, Penh value (% baseline) was measured using a whole-body plethysmograph.
In this study using ovalbumin-induced asthmatic mice, we observed that intraperitoneal injection of IL-35 during the allergen sensitization stage was more efficient than administration in the challenge stage for the amelioration of airway hyper-responsiveness. This was reflected by the significantly reduced concentration of asthma-related Th2 cytokines IL-5 and IL-13, as well as eosinophil counts in bronchoalveolar lavage fluid (all P < 0.05). IL-35 also significantly attenuated the accumulation of migratory CD11b+CD103(-) dendritic cells (DC) in the mediastinal lymph node (mLN) and lung of mice (all P < 0.05). IL-35 markedly inhibited the ovalbumin-induced conversion of recruited monocytes into inflammatory DC, which were then substantially reduced in mLN to cause less T-cell proliferation (all P < 0.05). Further study using the humanized asthmatic murine model also indicated human IL-35 exhibited a regulatory impact on allergic asthma.
Our findings suggest that IL-35 can act as a crucial regulatory cytokine to inhibit the development of allergic airway inflammation via suppressing the formation of inflammatory DC at the inflammatory site and their accumulation in the draining lymph nodes.
IL-35 是 IL-12 家族的新成员，是由调节性 T 和 B 淋巴细胞产生的抑制性细胞因子，在炎症性疾病中发挥抑制作用。本研究专注于调节 IL-35 在哮喘小鼠中抗炎活性的细胞机制。
采用卵清蛋白诱导的哮喘和人源化哮喘小鼠来评估 IL-35 的体内抗炎活性。为了监测气道，使用全身 plethysmograph 测量 Penh 值（%基础值）。
在本研究中，我们使用卵清蛋白诱导的哮喘小鼠发现，在致敏阶段腹腔内注射 IL-35 比在激发阶段给药更能改善气道高反应性。这反映在哮喘相关 Th2 细胞因子 IL-5 和 IL-13 的浓度以及支气管肺泡灌洗液中的嗜酸性粒细胞计数显著降低（均 P<0.05）。IL-35 还显著减弱了迁移性 CD11b+CD103(-)树突状细胞（DC）在纵隔淋巴结（mLN）和肺中的积聚（均 P<0.05）。IL-35 明显抑制了招募的单核细胞向炎症性 DC 的转化，从而导致 mLN 中的炎症性 DC 减少，进而引起 T 细胞增殖减少（均 P<0.05）。使用人源化哮喘小鼠模型的进一步研究也表明，人 IL-35 对过敏性哮喘具有调节作用。
我们的研究结果表明，IL-35 可以作为一种关键的调节性细胞因子，通过抑制炎症部位炎症性 DC 的形成及其在引流淋巴结中的积聚，抑制过敏性气道炎症的发展。
