Basic and Applied Immunology Program, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Sao Paulo, Brazil.
Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Sao Paulo, Brazil.
Int J Mol Sci. 2023 Jun 21;24(13):10418. doi: 10.3390/ijms241310418.
There is evidence that IL-22 and IL-17 participate in the pathogenesis of allergic asthma. To investigate the role of IL-22, we used IL-22 deficient mice (IL-22 KO) sensitized and challenged with ovalbumin (OVA) and compared with wild type (WT) animals exposed to OVA. IL-22 KO animals exposed to OVA showed a decreased number and frequency of eosinophils, IL-5 and IL-13 in the airways, reduced mucus production and pulmonary inflammation. In addition, IL-22 KO animals exhibited a decreased percentage and number of lung CD11cCD11b cells and increased apoptosis of eosinophils. Th17 cell transfer generated from IL-22 KO to animals previously sensitized and challenged with OVA caused a reduction in eosinophil frequency and number in the airways compared to animals transferred with Th17 cells generated from WT mice. Therefore, IL-22 is deleterious with concomitant secretion of IL-17. Our findings show a pro-inflammatory role for IL-22, confirmed in a model of allergen-free and allergen-specific immunotherapy. Moreover, during the comorbidity asthma and pneumonia that induces neutrophil inflammation, IL-22 was not detrimental. Our results show that targeting IL-22 would negatively affect the survival of eosinophils, reduce the expansion or migration of CD11cCD11b cells, and negatively regulate allergic asthma.
有证据表明，IL-22 和 IL-17 参与了过敏性哮喘的发病机制。为了研究 IL-22 的作用，我们使用了 IL-22 缺陷小鼠（IL-22 KO）进行卵清蛋白（OVA）致敏和激发，并与暴露于 OVA 的野生型（WT）动物进行比较。暴露于 OVA 的 IL-22 KO 动物表现出气道中嗜酸性粒细胞、IL-5 和 IL-13 的数量和频率减少，黏液产生和肺部炎症减少。此外，IL-22 KO 动物表现出肺 CD11cCD11b 细胞的百分比和数量减少，以及嗜酸性粒细胞凋亡增加。从 IL-22 KO 转移到先前用 OVA 致敏和激发的动物的 Th17 细胞转移导致气道中嗜酸性粒细胞频率和数量减少，与从 WT 小鼠产生的 Th17 细胞转移的动物相比。因此，IL-22 与 IL-17 的同时分泌具有有害作用。我们的研究结果显示，IL-22 在过敏原非特异性和过敏原特异性免疫治疗的模型中具有促炎作用。此外，在诱导中性粒细胞炎症的哮喘和肺炎合并症中，IL-22 没有造成损害。我们的结果表明，靶向 IL-22 会对嗜酸性粒细胞的存活产生负面影响，减少 CD11cCD11b 细胞的扩增或迁移，并负性调节过敏性哮喘。
