中文摘要:粘膜疫苗是防治传染病的一种有效手段,对粘膜疫苗的优化能够产生最优的免疫保护反应。粘膜屏障是防御许多病原的第一道防线。因此研究重点研究粘膜屏障的生物学特征从而提高疫苗的传递效率。IL-22是正常或炎性粘膜组织的一个重要细胞因子,能够促进上皮细胞增殖、抑制细胞凋亡、上调黏液素和抗菌肽,从而保证粘膜屏障的完整性。研发表明,粘膜免疫过程中,IL-22会损害T细胞反应。与野生小鼠相比,采用蛋白和霍乱毒素直肠内免疫的IL-22缺陷型小鼠产生的抗原特异性CD4 T细胞反应增强。当用明矾吸附的同种抗原进行系统免疫时,IL-22与野生型小鼠产生的CD4 T细胞反应无差异。这表明,在进行粘膜免疫时,瞬时抑制IL-22表达能够增强T细胞反应。这一方法的广泛适用于现有的黏膜疫苗疗法,且更有效的粘膜疫苗研发领域具有广阔的应用前景。
外文摘要:Mucosal vaccines are a promising platform for combatting infectious diseases for which we still lack effective preventative measures. Optimizing these vaccines to generate the best protective immune responses with the least complicated immunization regimen is imperative. Mucosal barriers are the first line of defense against many pathogens and, as such, we looked to their biology for strategies to improve vaccine delivery. Interleukin-22 (IL-22) is a key cytokine in both healthy and inflamed mucosal tissues. IL-22 promotes epithelial cell proliferation and inhibits apoptosis, upregulates mucin and antimicrobial peptides, all of which promote mucosal barrier integrity. In this study, we find that IL-22 impairs the development of a T cell response during mucosal immunization. Compared to wild-type control mice, 1L-22 deficient mice had increased antigen-specific CD4 T cell responses to intrarectal immunization using a protein and cholera toxin adjuvant vaccine. When immunized systemically with the same protein antigen adsorbed to alum, no differences in the CD4 T cell response between wild-type and 1L-22 deficient mice were detected. This suggests that transiently inhibiting IL-22 during mucosal vaccination could enhance T cell responses. The broad-applicability of this proposed approach would allow for improvement of many existing mucosal vaccine regimens and have positive implications in the development of more efficacious mucosal vaccines.
外文关键词:Cytokines; Mucosal vaccination; CD4 T cells
作者:Budda, SA; Zenewicz, LA
作者单位:美国奥克拉荷马大学
期刊名称:VACCINE
期刊影响因子:2.327
出版年份:2018
出版刊次:6
点击下载:IL-22敲除可增强粘膜免疫的CD4T细胞反应