Differential Regulation of Allergic Airway Inflammation by Acetylcholine.
Differential Regulation of Allergic Airway Inflammation by Acetylcholine.
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乙酰胆碱对变应性气道炎症的差异调节。
DOI：
10.3389/fimmu.2022.893844
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
来自神经元和非神经元来源的乙酰胆碱（ACh）在免疫应答的调节中起重要作用，并且与若干疾病病理学的发展相关。我们以前已经证明，第2组先天淋巴细胞（ILC 2）衍生的ACh是需要最佳的2型反应寄生虫感染，因此试图确定这是否也在过敏性炎症中发挥作用。将Rora Cre+ Chat LoxP小鼠（其中ILC 2不能合成ACh）暴露于真菌链格孢菌（Alternaria alternata）的过敏性提取物，并分析气道和肺组织中的免疫反应。暴露后24 h，气道嗜中性粒细胞和中性粒细胞趋化因子CXCL 1和CXCL 2的表达增强，表明ILC 2衍生的ACh在限制过度的肺嗜中性粒细胞炎症中起作用。非选择性消耗乙酰胆碱的影响进行了研究，通过鼻内给药的一个稳定的寄生虫分泌的乙酰胆碱酯酶。以这种方式消耗气道ACh导致嗜中性粒细胞和趋化因子表达的更深刻的增强，这表明ACh的释放有多种细胞来源。相比之下，ACh的耗尽可抑制链格孢菌诱导的ILC 2激活，抑制IL-5、IL-13的表达以及随后的嗜酸性粒细胞增多。消耗乙酰胆碱减少巨噬细胞的交替激活M2表型和M1巨噬细胞标志物表达的增加。这些数据表明，乙酰胆碱调节过敏性气道炎症在几个方面，提高ILC 2驱动的嗜酸性粒细胞增多症，但抑制嗜酸性粒细胞减少趋化因子的表达。
Acetylcholine (ACh) from neuronal and non-neuronal sources plays an important role in the regulation of immune responses and is associated with the development of several disease pathologies. We have previously demonstrated that group 2 innate lymphoid cell (ILC2)-derived ACh is required for optimal type 2 responses to parasitic infection and therefore sought to determine whether this also plays a role in allergic inflammation. Rora Cre+ Chat LoxP mice (in which ILC2s cannot synthesize ACh) were exposed to an allergenic extract of the fungus Alternaria alternata, and immune responses in the airways and lung tissues were analyzed. Airway neutrophilia and expression of the neutrophil chemoattractants CXCL1 and CXCL2 were enhanced 24 h after exposure, suggesting that ILC2-derived ACh plays a role in limiting excessive pulmonary neutrophilic inflammation. The effect of non-selective depletion of ACh was examined by intranasal administration of a stable parasite-secreted acetylcholinesterase. Depletion of airway ACh in this manner resulted in a more profound enhancement of neutrophilia and chemokine expression, suggesting multiple cellular sources for the release of ACh. In contrast, depletion of ACh inhibited Alternaria-induced activation of ILC2s, suppressing the expression of IL-5, IL-13, and subsequent eosinophilia. Depletion of ACh reduced macrophages with an alternatively activated M2 phenotype and an increase in M1 macrophage marker expression. These data suggest that ACh regulates allergic airway inflammation in several ways, enhancing ILC2-driven eosinophilia but suppressing neutrophilia through reduced chemokine expression.