调节性B和T细胞在蠕虫寄生诱导的对过敏性气道炎症中的关键作用
2020/02/11
摘要
过敏性哮喘的患病率与人类蠕虫感染的发生率呈负相关。尽管实验研究已经建立了寄生虫感染与过敏性哮喘之间的因果关系，但仍未完全阐明寄生虫相关免疫调节的机制。使用哮喘和多形螺旋线虫的小鼠模型，我们研究了调节性B细胞（B）和T细胞（T）在介导寄生虫对过敏性哮喘的保护中的作用。肺组织病理学上的改善和支气管肺泡炎性细胞浸润数量的减少可证明，多形螺旋线虫感染显着抑制了卵清蛋白（OVA）诱导的变应性气道炎症（AAI），并诱导了白介素IL-10 B，IL-10 T和小鼠肠系膜淋巴结和脾中的FoxP3 T细胞。 IL-10 B和IL-10 T细胞的过继转移阻止了变应性气道炎症小鼠的肺免疫病理。白喉毒素（DT）处理导致FoxP3-白喉毒素（DT）受体转基因小鼠中的FoxP3 T细胞耗尽，这加剧了无寄生虫AAI小鼠的气道炎症，并部分废除了寄生虫诱发的针对变应性气道炎症的保护作用。IL-10 B细胞能够促进IL-10 T扩增并维持FoxP3 T细胞数量。这两种类型的T无法诱导CD19 B细胞转化为IL-10 B细胞。这些结果表明，B、IL-10 T和FoxP3 T细胞以不同的方式参与了寄生虫带来的保护作用以对抗过敏气道的免疫病理学改变。B细胞可能是诱导IL-10 T反应并维持FoxP3 T细胞数量的关键性上游调节细胞，而FoxP3 T细胞也能够介导寄生虫强行带来的对过敏性气道炎症的免疫抑制。这些结果提供了对寄生虫感染和过敏性哮喘之间免疫学关系的深刻理解。
Critical roles of regulatory B and T cells in helminth parasite-induced protection against allergic airway inflammation.
Gao X, et al., Clin Exp Allergy. 2019 Aug 9.
Abstract
The prevalence of allergic asthma and incidences of helminth infections in humans are inversely correlated. Although experimental studies have established the causal relation between parasite infection and allergic asthma, the mechanism of the parasite-associated immunomodulation is not fully elucidated. Using a murine model of asthma and nematode parasite Heligmosomoides polygyrus, we investigated the roles of regulatory B cells (B ) and T cells (T ) in mediation of the protection against allergic asthma by parasite. H. polygyrus infection significantly suppressed ovalbumin (OVA)-induced allergic airway inflammation (AAI) evidenced by alleviated lung histopathology and reduced numbers of bronchoalveolar inflammatory cell infiltration, and induced significant responses of interleukin (IL)-10 B , IL-10 T and forkhead box protein 3 (FoxP3) T in mesenteric lymph node and spleen of the mice. Adoptive transfer of IL-10 B and IL-10 T cell prevented the lung immunopathology in AAI mice. Depletion of FoxP3 T cells in FoxP3-diphtheria toxin (DT) receptor transgenic mice by diphtheria toxin (DT) treatment exacerbated airway inflammation in parasite-free AAI mice and partially abrogated the parasite-induced protection against AAI. IL-10 B cells were able to promote IL-10 T expansion and maintain FoxP3 T cell population. These two types of T failed to induce CD19 B cells to transform into IL-10 B cells. These results demonstrate that B , IL-10 T and FoxP3 T cells contribute in A discrepant manner to the protection against allergic airway immunopathology by parasiteS. B cell might be a key upstream regulatory cell that induces IL-10 T response and supports FoxP3 T cell population which, in turn, mediate the parasite-imposed immunosuppression of allergic airway inflammation. These results provide insight into the immunological relationship between parasite infection and allergic asthma.
过敏性哮喘的患病率与人类蠕虫感染的发生率呈负相关。尽管实验研究已经建立了寄生虫感染与过敏性哮喘之间的因果关系，但仍未完全阐明寄生虫相关免疫调节的机制。使用哮喘和多形螺旋线虫的小鼠模型，我们研究了调节性B细胞（B）和T细胞（T）在介导寄生虫对过敏性哮喘的保护中的作用。肺组织病理学上的改善和支气管肺泡炎性细胞浸润数量的减少可证明，多形螺旋线虫感染显着抑制了卵清蛋白（OVA）诱导的变应性气道炎症（AAI），并诱导了白介素IL-10 B，IL-10 T和小鼠肠系膜淋巴结和脾中的FoxP3 T细胞。 IL-10 B和IL-10 T细胞的过继转移阻止了变应性气道炎症小鼠的肺免疫病理。白喉毒素（DT）处理导致FoxP3-白喉毒素（DT）受体转基因小鼠中的FoxP3 T细胞耗尽，这加剧了无寄生虫AAI小鼠的气道炎症，并部分废除了寄生虫诱发的针对变应性气道炎症的保护作用。IL-10 B细胞能够促进IL-10 T扩增并维持FoxP3 T细胞数量。这两种类型的T无法诱导CD19 B细胞转化为IL-10 B细胞。这些结果表明，B、IL-10 T和FoxP3 T细胞以不同的方式参与了寄生虫带来的保护作用以对抗过敏气道的免疫病理学改变。B细胞可能是诱导IL-10 T反应并维持FoxP3 T细胞数量的关键性上游调节细胞，而FoxP3 T细胞也能够介导寄生虫强行带来的对过敏性气道炎症的免疫抑制。这些结果提供了对寄生虫感染和过敏性哮喘之间免疫学关系的深刻理解。
（中国医科大学附属第一医院 李文扬 摘译 杨冬 审校）
（Gao X, et al., Clin Exp Allergy. 2019 Aug 9.）
（Gao X, et al., Clin Exp Allergy. 2019 Aug 9.）
Critical roles of regulatory B and T cells in helminth parasite-induced protection against allergic airway inflammation.
Gao X, et al., Clin Exp Allergy. 2019 Aug 9.
Abstract
The prevalence of allergic asthma and incidences of helminth infections in humans are inversely correlated. Although experimental studies have established the causal relation between parasite infection and allergic asthma, the mechanism of the parasite-associated immunomodulation is not fully elucidated. Using a murine model of asthma and nematode parasite Heligmosomoides polygyrus, we investigated the roles of regulatory B cells (B ) and T cells (T ) in mediation of the protection against allergic asthma by parasite. H. polygyrus infection significantly suppressed ovalbumin (OVA)-induced allergic airway inflammation (AAI) evidenced by alleviated lung histopathology and reduced numbers of bronchoalveolar inflammatory cell infiltration, and induced significant responses of interleukin (IL)-10 B , IL-10 T and forkhead box protein 3 (FoxP3) T in mesenteric lymph node and spleen of the mice. Adoptive transfer of IL-10 B and IL-10 T cell prevented the lung immunopathology in AAI mice. Depletion of FoxP3 T cells in FoxP3-diphtheria toxin (DT) receptor transgenic mice by diphtheria toxin (DT) treatment exacerbated airway inflammation in parasite-free AAI mice and partially abrogated the parasite-induced protection against AAI. IL-10 B cells were able to promote IL-10 T expansion and maintain FoxP3 T cell population. These two types of T failed to induce CD19 B cells to transform into IL-10 B cells. These results demonstrate that B , IL-10 T and FoxP3 T cells contribute in A discrepant manner to the protection against allergic airway immunopathology by parasiteS. B cell might be a key upstream regulatory cell that induces IL-10 T response and supports FoxP3 T cell population which, in turn, mediate the parasite-imposed immunosuppression of allergic airway inflammation. These results provide insight into the immunological relationship between parasite infection and allergic asthma.
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