PDF(Pubmed)
Abstract：
UNASSIGNED: Allergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to current treatment protocols. Therefore, there is a need for deeper mechanistic insights and further improvement of treatment strategies. The relevance of the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, has been investigated in several inflammatory diseases, including allergic asthma. However, its potential role in AIT still needs to be addressed.
UNASSIGNED: A murine model of AIT in ovalbumin-induced allergic airway inflammation was performed in AhR-deficient (AhR-/-) and wild-type mice. Furthermore, AIT was combined with the application of the high-affinity AhR agonist 10-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ) as an adjuvant to investigate the effects of AhR activation on therapeutic outcome.
UNASSIGNED: Although AhR-/- mice suffer stronger allergic responses than wild-type mice, experimental AIT is comparably effective in both. Nevertheless, combining AIT with the administration of 10-Cl-BBQ improved therapeutic effects by an AhR-dependent mechanism, resulting in decreased cell counts in the bronchoalveolar fluid, decreased pulmonary Th2 and Th17 cell levels, and lower sIgE levels.
UNASSIGNED: This study demonstrates that the success of AIT is not dependent on the AhR. However, targeting the AhR during AIT can help to dampen inflammation and improve tolerogenic vaccination. Therefore, AhR ligands might represent promising candidates as immunomodulators to enhance the efficacy of AIT.
UNASSIGNED: A murine model of AIT in ovalbumin-induced allergic airway inflammation was performed in AhR-deficient (AhR-/-) and wild-type mice. Furthermore, AIT was combined with the application of the high-affinity AhR agonist 10-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ) as an adjuvant to investigate the effects of AhR activation on therapeutic outcome.
UNASSIGNED: Although AhR-/- mice suffer stronger allergic responses than wild-type mice, experimental AIT is comparably effective in both. Nevertheless, combining AIT with the administration of 10-Cl-BBQ improved therapeutic effects by an AhR-dependent mechanism, resulting in decreased cell counts in the bronchoalveolar fluid, decreased pulmonary Th2 and Th17 cell levels, and lower sIgE levels.
UNASSIGNED: This study demonstrates that the success of AIT is not dependent on the AhR. However, targeting the AhR during AIT can help to dampen inflammation and improve tolerogenic vaccination. Therefore, AhR ligands might represent promising candidates as immunomodulators to enhance the efficacy of AIT.
摘要：
■过敏原特异性免疫疗法（AIT）能够恢复过敏患者对过敏原的免疫耐受。然而,一些患者对目前的治疗方案没有反应或仅反应不佳.因此,需要更深入的机械见解和进一步改进治疗策略.芳烃受体（AhR）的相关性，配体依赖性转录因子，已经在几种炎症性疾病中进行了研究，包括过敏性哮喘.然而,它在AIT中的潜在作用仍需解决。
在AhR缺陷(AhR-/-)和野生型小鼠中进行卵清蛋白诱导的过敏性气道炎症中的AIT的小鼠模型。此外，AIT与高亲和力AhR激动剂10-氯-7H-苯并咪唑并[2,1-a]苯并[de]异喹啉-7-酮（10-Cl-BBQ）作为佐剂的应用相结合，以研究AhR活化对治疗结果的影响。
■尽管AhR-/-小鼠的过敏反应比野生型小鼠更强，实验性AIT在这两个方面都相当有效。然而，将AIT与10-Cl-BBQ的给药相结合，通过AhR依赖性机制改善了治疗效果，导致支气管肺泡液中的细胞计数减少，肺Th2和Th17细胞水平降低，降低sIgE水平。
■这项研究表明，AIT的成功与AhR无关。然而,在AIT期间靶向AhR可以帮助抑制炎症并改善耐受性疫苗接种。因此,AhR配体可能代表有希望的候选物作为免疫调节剂以增强AIT的功效。
在AhR缺陷(AhR-/-)和野生型小鼠中进行卵清蛋白诱导的过敏性气道炎症中的AIT的小鼠模型。此外，AIT与高亲和力AhR激动剂10-氯-7H-苯并咪唑并[2,1-a]苯并[de]异喹啉-7-酮（10-Cl-BBQ）作为佐剂的应用相结合，以研究AhR活化对治疗结果的影响。
■尽管AhR-/-小鼠的过敏反应比野生型小鼠更强，实验性AIT在这两个方面都相当有效。然而，将AIT与10-Cl-BBQ的给药相结合，通过AhR依赖性机制改善了治疗效果，导致支气管肺泡液中的细胞计数减少，肺Th2和Th17细胞水平降低，降低sIgE水平。
■这项研究表明，AIT的成功与AhR无关。然而,在AIT期间靶向AhR可以帮助抑制炎症并改善耐受性疫苗接种。因此,AhR配体可能代表有希望的候选物作为免疫调节剂以增强AIT的功效。
