蛋白介導(dǎo)CD11c高表達(dá)巨噬細(xì)胞的預(yù)編程抗炎表型保護(hù)過(guò)敏性哮喘

2023年12月，重慶醫(yī)科大學(xué)檢驗(yàn)醫(yī)學(xué)院檢驗(yàn)醫(yī)學(xué)診斷教育部重點(diǎn)實(shí)驗(yàn)室，重慶400016;遵義市第一人民醫(yī)院(遵義醫(yī)科大學(xué)第三附屬醫(yī)院)檢驗(yàn)醫(yī)學(xué)科(Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China；Department of Laboratory Medicine, The First People’s Hospital of Zunyi City (The Third Afliated Hospital of Zunyi Medical University)) Bingyan Wu老師研究團(tuán)隊(duì)在《Journal of Translational Medicine》上發(fā)表論文：

 “The preprogrammed anti-inflammatory phenotypes of CD11chigh macrophages by Streptococcus pneumoniae aminopeptidase N safeguard from allergic asthma"

“肺炎鏈球菌氨基肽酶N介導(dǎo)CD11c高表達(dá)巨噬細(xì)胞的預(yù)編程抗炎表型保護(hù)過(guò)敏性哮喘"

Abstract：

Background: Early microbial exposure is associate with protective allergic asthma. We have previously demonstrated that Streptococcus pneumoniae aminopeptidase N (PepN), one of the pneumococcal components, inhibits ovalbumin (OVA) -induced airway inflammation in murine models of allergic asthma, but the underlying mechanism was incompletely determined.

Methods: BALB/c mice were pretreated with the PepN protein and exposed intranasally to HDM allergen. The anti-inflammatory mechanisms were investigated using depletion and adoptive transfer experiments as well as transcriptome analysis and isolated lung CD11chigh macrophages.

Results: We found pretreatment of mice with PepN promoted the proliferation of lung-resident F4/80+CD11chigh macrophages in situ but also mobilized bone marrow monocytes to infiltrate lung tissue that were then transformed into CD11high macrophages. PepN pre-programmed the macrophages during maturation to an anti-inflammatory phenotype by shaping the metabolic preference for oxidative phosphorylation (OXPHOS) and also inhibited the inflammatory response of macrophages by activating AMP-activated protein kinase. Furthermore, PepN treated macrophages also exhibited high-level costimulatory signaling molecules which directed the differentiation into Treg.

Conclusion: Our results demonstrated that the expansion of CD11chigh macrophages in lungs and the OXPHOS metabolic bias of macrophages are associated with reduced allergic airway inflammation after PepN exposure, which paves the way for its application in preventing allergic asthma.

摘要：

背景:早期微生物暴露與保護(hù)性過(guò)敏性哮喘有關(guān)。研究人員之前已經(jīng)證明肺炎鏈球菌氨基肽酶N (PepN)是一種肺炎球菌成分，在小鼠過(guò)敏性哮喘模型中抑制卵清蛋白(OVA)誘導(dǎo)的氣道炎癥，但其潛在機(jī)制尚不確定。

方法:用PepN蛋白預(yù)處理BALB/c小鼠，鼻內(nèi)暴露HDM變應(yīng)原。通過(guò)耗竭和過(guò)繼轉(zhuǎn)移實(shí)驗(yàn)以及轉(zhuǎn)錄組分析和分離的肺cd11高巨噬細(xì)胞來(lái)研究其抗炎機(jī)制。

結(jié)果:研究人員發(fā)現(xiàn)用PepN預(yù)處理小鼠可促進(jìn)肺內(nèi)F4/80+ cd11高巨噬細(xì)胞的原位增殖，并可動(dòng)員骨髓單核細(xì)胞浸潤(rùn)肺組織，然后轉(zhuǎn)化為cd11高巨噬細(xì)胞。PepN通過(guò)塑造氧化磷酸化(OXPHOS)的代謝偏好，在巨噬細(xì)胞成熟過(guò)程中預(yù)編程為抗炎表型，并通過(guò)激活amp激活的蛋白激酶抑制巨噬細(xì)胞的炎癥反應(yīng)。此外，PepN處理的巨噬細(xì)胞也表現(xiàn)出高水平的共刺激信號(hào)分子，引導(dǎo)分化為Treg。

結(jié)論:研究人員的研究結(jié)果表明，肺中cd11高的巨噬細(xì)胞的擴(kuò)張和巨噬細(xì)胞的OXPHOS代謝偏倚與PepN暴露后過(guò)敏性氣道炎癥的減少有關(guān)，這為其在預(yù)防過(guò)敏性哮喘中的應(yīng)用奠定了基礎(chǔ)。

該論文中，6-8周齡C57BL/6 J小鼠BMDMs（骨髓源性巨噬細(xì)胞）的體外培養(yǎng)是使用Ausbian特級(jí)胎牛血清完成的。