Allergic Asthma Responses Are Dependent on Macrophage Ontogeny.
Allergic Asthma Responses Are Dependent on Macrophage Ontogeny.
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过敏性哮喘反应取决于巨噬细胞个体发育。
DOI：
10.1101/2023.02.16.528861
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Yu
中科院分区：
文献类型：
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作者：
Tighe,RobertM;Birukova,Anastasiya;Malakhau,Yuryi;Kobayashi,Yoshihiko;Vose,AaronT;Chandramohan,Vidya;Cyphert-Daly,JaimeM;Cumming,RIan;Kirshner,HeleneFradin;Tata,PurushothamaR;Ingram,JenniferL;Gunn,MichaelD;Que,LorettaG;Yu
损伤、环境暴露或实验耗竭后组织驻留巨噬细胞的个体发育组成可以在体内平衡重建后发生改变。然而，改变的常驻巨噬细胞个体发生环境对随后的免疫反应的影响尚不清楚。因此，我们评估了恢复稳态后巨噬细胞个体发育改变对随后对屋尘螨（HDM）的过敏性气道反应的影响。通过谱系追踪，我们证实了肺泡和间质巨噬细胞的个体发育，以及在 LPS 暴露后它们被骨髓源性巨噬细胞取代。巨噬细胞个体发生环境的这种改变减少了对 HDM 挑战的过敏性气道反应。此外，我们定义了一个独特的居民源性间质巨噬细胞群体，表达过敏性气道疾病基因，位于末梢支气管附近，并因之前的 LPS 暴露而减少。这些发现支持肺巨噬细胞的个体发育环境是过敏性气道反应的核心因素，并且对于先前的环境暴露如何影响随后的免疫反应和过敏的发展具有影响。
The ontogenetic composition of tissue-resident macrophages following injury, environmental exposure, or experimental depletion can be altered upon re-establishment of homeostasis. However, the impact of altered resident macrophage ontogenetic milieu on subsequent immune responses is poorly understood. Hence, we assessed the effect of macrophage ontogeny alteration following return to homeostasis on subsequent allergic airway responses to house dust mites (HDM). Using lineage tracing, we confirmed alveolar and interstitial macrophage ontogeny and their replacement by bone marrow-derived macrophages following LPS exposure. This alteration in macrophage ontogenetic milieu reduced allergic airway responses to HDM challenge. In addition, we defined a distinct population of resident-derived interstitial macrophages expressing allergic airway disease genes, located adjacent to terminal bronchi, and reduced by prior LPS exposure. These findings support that the ontogenetic milieu of pulmonary macrophages is a central factor in allergic airway responses and has implications for how prior environmental exposures impact subsequent immune responses and the development of allergy.