Oral antibiotics relieve allergic asthma in post-weaning mice via reducing iNKT cells and function of ADRB2.
Oral antibiotics relieve allergic asthma in post-weaning mice via reducing iNKT cells and function of ADRB2.
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口服抗生素通过减少 iNKT 细胞和 ADRB2 功能缓解断奶后小鼠过敏性哮喘
DOI：
10.3389/fimmu.2022.1024235
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发表时间：
2022
影响因子：
7.3
通讯作者：
Su, Xiao
中科院分区：
文献类型：
--
作者：
Li, Na;Chen, Jie;Xie, Sitao;Zhang, Meng;Shi, Tianyun;He, Yanchao;Jie, Zhijun;Su, Xiao
正常肠道微生物区系在哮喘或卵清蛋白(OVA)诱导的哮喘耐受(OT)中的作用尚不清楚。在这里，我们建立了哮喘和OT的小鼠模型，然后进行2周的抗生素治疗，以清除肠道微生物区系。抗生素治疗被发现可以缓解过敏性哮喘，同时伴有不变自然杀伤(INKT)细胞的减少。通过序列分析，我们发现β肾上腺素能受体基因在哮喘肺组织中表达下调，而在OT肺组织中表达下调。此外，经抗生素治疗后，哮喘大鼠肺组织中ADRB2和ADRB3的表达显著上调。令人惊讶的是，用心得安阻断ADRB可以缓解过敏性哮喘，同时减少辅助性T细胞(Th2)和Treg细胞数量。进一步的流式细胞仪和免疫荧光分析表明，哮喘肺组织中ADRB2的蛋白表达水平高于正常对照组和OT肺组织。值得注意的是，哮喘肺中树突状细胞(DC)，尤其是ADRB2+DC较对照组和OT肺明显增多。此外，给予ADRB2特异性拮抗剂ICI118551后，ADRB2+DC显著减少。我们的研究结果表明，抗生素治疗可以通过降低iNKT细胞的频率和ADRB2的功能来减轻OVA诱导的过敏性哮喘。
The role of normal gut microbiota in asthma or ovalbumin (OVA)-induced asthma tolerance (OT) remains unclear. Here, we established mouse models of asthma and OT followed by 2 weeks of antibiotic treatment, to clear the gut microbiota. Antibiotic treatment was found to alleviate allergic asthma accompanied with a reduction of invariant natural killer (iNKT) cells. By RNA-seq analysis, we found that β-adrenergic receptor (ADRB) genes, including Adrb1, Adrb2, and Adrb3, were downregulated in asthmatic lungs, but these changes were reversed in OT lungs. Moreover, Adrb2 and Adrb3 were significantly upregulated in asthmatic lungs after antibiotic treatment. Surprisingly, blocking ADRB with propranolol relieved allergic asthma while reducing T helper 2 (Th2) and Treg cell numbers. Further analyses using flow cytometry and immunofluorescence showed that the protein expression level of ADRB2 was higher in asthmatic lungs than that in the control and OT lungs. Notably, dendritic cells (DCs), especially the ADRB2+ DCs, were increased in asthmatic lungs compared to that in the control and OT lungs. In addition, ADRB2+ DCs were significantly reduced following the administration of the ADRB2-specific antagonist ICI118551. Our findings suggest that antibiotic treatment can alleviate OVA-induced allergic asthma via reducing the frequency of iNKT cells and function of ADRB2.
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影响因子：
7.3
作者：
Al-Kuraishy HM;Al-Gareeb AI;Mostafa-Hedeab G;Kasozi KI;Zirintunda G;Aslam A;Allahyani M;Welburn SC;Batiha GE
通讯作者：
Batiha GE
影响因子：
168.9
作者：
Jones, Stacie M.;Kim, Edwin H.;Nadeau, Kari C.;Nowak-Wegrzyn, Anna;Wood, Robert A.;Sampson, Hugh A.;Scurlock, Amy M.;Chinthrajah, Sharon;Wang, Julie;Pesek, Robert D.;Sindher, Sayantani B.;Kulis, Mike;Johnson, Jacqueline;Spain, Katharine;Babineau, Denise C.;Chin, Hyunsook;Laurienzo-Panza, Joy;Yan, Rachel;Larson, David;Qin, Tian;Whitehouse, Don;Sever, Michelle L.;Sanda, Srinath;Plaut, Marshall;Wheatley, Lisa M.;Burks, A. Wesley
通讯作者：
Burks, A. Wesley
影响因子：
8
作者：
Cait, A.;Hughes, M. R.;Mohn, W. W.
通讯作者：
Mohn, W. W.
影响因子：
64.8
作者：
Esterhazy, Daria;Canesso, Maria C. C.;Mucida, Daniel
通讯作者：
Mucida, Daniel
影响因子：
3.8
作者：
Lopez, Soledad;Gomez, Enrique;Mayorga, Cristobalina
通讯作者：
Mayorga, Cristobalina