Lee Chang Hoon, Hajishengallis George, Connell Terry D
Bio & Drug Discovery Division, Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.
Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34114, Republic of Korea.
J Microbiol Biotechnol. 2017 Apr 28;27(4):709-717. doi: 10.4014/jmb.1611.11072.
Mucosal tissues are the initial site through which most pathogens invade. As such, vaccines and adjuvants that modulate mucosal immune functions have emerged as important agents for disease prevention. Herein, we investigated the immunomodulatory mechanisms of the B subunit of heat-labile enterotoxin type IIa (LT-IIa-B), a potent non-toxic mucosal adjuvant. Alternations in gene expression in response to LT-IIa-B were identified using a genome-wide transcriptional microarray that focused on dendritic cells (DC), a type of cell that broadly orchestrates adaptive and innate immune responses. We found that LT-IIa-B enhanced the homing capacity of DC into the lymph nodes and selectively regulated transcription of pro-inflammatory cytokines, chemokines, and cytokine receptors. These data are consistent with a model in which directional activation and differentiation of immune cells by LT-IIa-B serve as a critical mechanism whereby this potent adjuvant amplifies mucosal immunity to co-administered antigens.
黏膜组织是大多数病原体侵入人体的初始部位。因此，调节黏膜免疫功能的疫苗和佐剂已成为疾病预防的重要手段。在此，我们研究了IIa型不耐热肠毒素（LT-IIa）的B亚基的免疫调节机制，它是一种有效的无毒黏膜佐剂。通过全基因组转录微阵列确定了对LT-IIa-B有反应的基因表达变化，该微阵列聚焦于树突状细胞（DC），这是一种广泛协调适应性免疫和先天性免疫反应的细胞类型。我们发现，LT-IIa-B增强了DC归巢至淋巴结的能力，并选择性地调节促炎细胞因子、趋化因子和细胞因子受体的转录。这些数据与一个模型一致，即LT-IIa-B对免疫细胞的定向激活和分化是这种有效佐剂增强对共同给药抗原的黏膜免疫的关键机制。
