Neuronal-Activated ILC2s Promote IL-17A Production in Lung γδ T Cells During Sepsis.
Neuronal-Activated ILC2s Promote IL-17A Production in Lung γδ T Cells During Sepsis.
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脓毒症期间神经元激活的 ILC2 促进肺 γ δ T 细胞产生 IL-17A
DOI：
10.3389/fimmu.2021.670676
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发表时间：
2021
影响因子：
7.3
通讯作者：
Shu Q
中科院分区：
文献类型：
--
作者：
Chen W;Lai D;Li Y;Wang X;Pan Y;Fang X;Fan J;Shu Q
研究已经揭示IL-17 A在脓毒症后急性肺损伤（ALI）的发展中的重要作用。然而，肺IL-17 A的调节机制仍有待充分解决。最近的研究表明，神经介肽U（NMU）对免疫细胞活化的作用和第2组先天淋巴细胞（ILC 2）在IL-17 A产生的调节中的作用。我们旨在深入了解脓毒症诱导的肺IL-17 A产生的机制，特别是NMU在脓毒症中介导ILC 2和IL-17 A产生γδ T细胞活化的神经元调节中的作用。在腹膜内注射或不注射NMU的情况下，对野生型小鼠进行盲肠结扎和穿孔（CLP）以诱导脓毒症。然后测量肺中ILC 2 ε、γδ T细胞、IL-17 A、NMU和NMU受体1（NMUR 1）的水平。为了确定NMU信号传导在ILC 2活化中的作用和ILC 2释放的IL-9在ILC 2-γδ T细胞相互作用中的作用，分选ILC 2，并使用CRISPR/Cas9敲低ILC 2中的nmur 1和il 9基因。然后将遗传操作的ILC 2与肺γδ T细胞共培养，并测量来自共培养系统的IL-17 A水平。在脓毒症小鼠中，肺中NMU、IL-17 A、ILC 2和产生IL-17 A的γδ T细胞的水平显著增加，并且ILC 2中NMUR 1的表达也增加。外源性NMU进一步增强了这些增加。IL-17 A在CLP应答中的主要来源是γδ T细胞，并且肺nmur 1在ILC 2中特异性表达。ILC 2 ε和γδ T细胞的体外共培养导致γδ T细胞数量增加和γδ T细胞产生更高的IL-17 A，并且这些改变通过脓毒症处理和外源性NMU进一步增强。ILC 2中nmur 1或il 9的基因敲低减弱了γδ T细胞和IL-17 A产生的上调。在脓毒症中，NMU通过肺ILC 2中的NMUR 1起作用，启动ILC 2活化，这反过来促进产生IL-17 A的γδ T细胞扩增和IL-17 A的分泌。ILC 2衍生的IL-9在介导γδ T细胞扩增和IL-17 A产生中起重要作用。本研究探讨了脓毒症中先天免疫的神经调节的新机制。
Studies have revealed important roles for IL-17A in the development of acute lung injury (ALI) following sepsis. However, the mechanism underlying the regulation of lung IL-17A remains to be fully addressed. Recent studies suggested the effect of neuromedin U (NMU) on immune cell activation and the role of group 2 innate lymphoid cells (ILC2s) in the modulation of IL-17A production. We aimed to gain in-depth insight into the mechanism underlying sepsis-induced lung IL-17A production, particularly, the role of NMU in mediating neuronal regulation of ILC2s and IL-17A-producing γδ T cells activation in sepsis. Wild type mice were subjected to cecal ligation and puncture (CLP) to induce sepsis with or without intraperitoneal injection of NMU. The levels of ILC2s, γδ T cells, IL-17A, NMU and NMU receptor 1 (NMUR1) in the lung were then measured. In order to determine the role of NMU signaling in ILC2 activation and the role of ILC2-released IL-9 in ILC2-γδ T cell interaction, ILC2s were sorted, and the genes of nmur1 and il9 in the ILC2s were knocked down using CRISPR/Cas9. The genetically manipulated ILC2s were then co-cultured with lung γδ T cells, and the levels of IL-17A from co-culture systems were measured. In septic mice, the levels of NMU, IL-17A, ILC2s, and IL-17A-producing γδ T cells in the lung are significantly increased, and the expression of NMUR1 in ILC2s is increased as well. Exogenous NMU further augments these increases. The main source of IL-17A in response to CLP is γδ T cells, and lung nmur1 is specifically expressed in ILC2s. In vitro co-culture of ILC2s and γδ T cells leads to increased number of γδ T cells and higher production of IL-17A from γδ T cells, and these alterations are further augmented by septic treatment and exogenous NMU. Genetic knockdown of nmur1 or il9 in ILC2s attenuated the upregulation of γδ T cells and IL-17A production. In sepsis, NMU acting through NMUR1 in lung ILC2s initiates the ILC2 activation, which, in turn, promote IL-17A-producing γδ T cell expansion and secretion of IL-17A. ILC2-derived IL-9 plays an important role in mediating γδ T cell expansion and IL-17A production. This study explores a new mechanism underlying neuronal regulation of innate immunity in sepsis.
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影响因子：
3.7
作者：
Gasse P;Riteau N;Vacher R;Michel ML;Fautrel A;di Padova F;Fick L;Charron S;Lagente V;Eberl G;Le Bert M;Quesniaux VF;Huaux F;Leite-de-Moraes M;Ryffel B;Couillin I
通讯作者：
Couillin I
影响因子：
16.6
作者：
Galle-Treger, Lauriane;Suzuki, Yuzo;Patel, Nisheel;Sankaranarayanan, Ishwarya;Aron, Jennifer L.;Maazi, Hadi;Chen, Lin;Akbari, Omid
通讯作者：
Akbari, Omid
产生 IL-17 ST2( ) 2 组先天淋巴细胞在肺部炎症中发挥致病作用
DOI：
10.1016/j.jaci.2018.03.007
发表时间：
2019-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Cai T;Qiu J;Ji Y;Li W;Ding Z;Suo C;Chang J;Wang J;He R;Qian Y;Guo X;Zhou L;Sheng H;Shen L;Qiu J
通讯作者：
Qiu J
影响因子：
4.6
作者：
Guggino, G.;Ciccia, F.;Triolo, G.
通讯作者：
Triolo, G.
影响因子：
4.8
作者：
Flierl, Michael A.;Rittirsch, Daniel;Ward, Peter A.
通讯作者：
Ward, Peter A.