调节性B细胞在变应原免疫治疗中的作用。
The role of regulatory B cells in allergen immunotherapy.
作者信息
van de Veen Willem
机构信息
aSwiss Institute of Allergy and Asthma Research, University of Zürich, Davos bChristine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
出版信息
Curr Opin Allergy Clin Immunol. 2017 Dec;17(6):447-452. doi: 10.1097/ACI.0000000000000400.
PURPOSE OF REVIEW
Allergen immunotherapy (AIT) is currently the only curative treatment available for allergic diseases, and has been used in clinical practice for over a century. Induction and maintenance of immune tolerance to nonhazardous environmental and self-antigens is essential to maintain homeostasis and prevent chronic inflammation. Regulatory B (BREG) cells are immunoregulatory cells that protect against chronic inflammatory responses primarily through production of anti-inflammatory cytokines such as IL-10, transforming growth factor-β, and IL-35. The importance of BREG cells has been extensively demonstrated in the context of autoimmune diseases. Data showing their role in the regulation of allergic responses are slowly accumulating. This review summarizes recent findings relevant to the topic of BREG cells and their potential role in AIT.
RECENT FINDINGS
BREG cells support AIT in models of allergic airway inflammation and intestinal inflammation through induction of regulatory T (TREG) cells. In humans BREG frequency increases during venom immunotherapy while the phenotype of allergen-specific B cells changes. Mechanisms of BREG-mediated tolerance to allergens include IL-10-mediated suppression of effector T cell, including TH2 responses, induction of TREG cells, IL-10-mediated inhibition of Dendritic cell maturation, modulation of T follicular helper responses, and production of anti-inflammatory IgG4 antibodies.
SUMMARY
Current evidence supports a potential role for BREG cells in induction and maintenance of allergen tolerance during AIT. A better understanding of the role of B cells and BREG cells in AIT could open potential new windows for developing targeted therapies specifically focused on promoting BREG responses during AIT.
综述目的
变应原免疫疗法(AIT)是目前唯一可用于治疗过敏性疾病的治愈性疗法,已在临床实践中应用了一个多世纪。诱导并维持对无害环境抗原和自身抗原的免疫耐受对于维持体内平衡和预防慢性炎症至关重要。调节性B(BREG)细胞是免疫调节细胞,主要通过产生抗炎细胞因子如白细胞介素-10(IL-10)、转化生长因子-β(TGF-β)和IL-35来预防慢性炎症反应。BREG细胞的重要性在自身免疫性疾病背景下已得到广泛证实。显示其在调节过敏反应中作用的数据正在缓慢积累。本综述总结了与BREG细胞主题及其在AIT中潜在作用相关的最新发现。
最新发现
在过敏性气道炎症和肠道炎症模型中,BREG细胞通过诱导调节性T(TREG)细胞来支持AIT。在人类中,毒液免疫疗法期间BREG频率增加,同时变应原特异性B细胞的表型发生变化。BREG介导的变应原耐受性机制包括IL-10介导的效应T细胞抑制,包括TH2反应、TREG细胞的诱导、IL-10介导的树突状细胞成熟抑制、T滤泡辅助反应的调节以及抗炎性IgG4抗体的产生。
总结
目前的证据支持BREG细胞在AIT期间诱导和维持变应原耐受性方面的潜在作用。更好地理解B细胞和BREG细胞在AIT中的作用可能为开发专门针对促进AIT期间BREG反应的靶向疗法打开潜在的新窗口。