Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function.
Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function.
复制标题
内皮素-A受体拮抗剂通过抑制ILC 2功能减轻过敏性气道炎症。
DOI：
10.3389/fimmu.2022.835953
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发表时间：
2022
影响因子：
7.3
通讯作者：
He Y
中科院分区：
文献类型：
--
作者：
Zhang X;Chen Z;Zuo S;Sun H;Li X;Lu X;Xing Z;Chen M;Liu J;Xiao G;He Y
过敏性气道炎症是一种普遍的气道疾病，是由吸入过敏原的高反应性驱动的。第2组先天性淋巴样细胞（ILC 2）产生大量的2型细胞因子，导致过敏性气道炎症。在这里，我们发现人和小鼠肺ILC 2的外周血都表达内皮素-A受体（ETAR），并且ETAR的表达水平在白细胞介素-33（IL-33）处理后显著诱导。随后，观察到ETAR拮抗剂BQ 123对过敏性气道炎症的预防和治疗作用，其与ILC 2的增殖和2型细胞因子产生减少有关。此外，发现来自BQ 123处理的ILC 2响应于白介素IL-33攻击而功能受损。BQ 123处理还影响了活化ILC 2中细胞外信号调节激酶（ERK）的磷酸化水平以及加塔结合蛋白3（GATA 3）的水平。有趣的是，在BQ 123处理后，小鼠和人ILC 2在体外均表现出降低的功能和ERK信号传导和GATA 3稳定性的下调。这些观察结果表明，ETAR是ILC 2功能的重要调节剂，并可能参与ILC 2驱动的肺部炎症。因此，阻断ETAR可能是治疗过敏性气道炎症的一种有前途的策略。
Allergic airway inflammation is a universal airway disease that is driven by hyperresponsiveness to inhaled allergens. Group 2 innate lymphoid cells (ILC2s) produce copious amounts of type 2 cytokines, which lead to allergic airway inflammation. Here, we discovered that both peripheral blood of human and mouse lung ILC2s express the endothelin-A receptor (ETAR), and the expression level of ETAR was dramatically induced upon interleukin-33 (IL-33) treatment. Subsequently, both preventive and therapeutic effects of BQ123, an ETAR antagonist, on allergic airway inflammation were observed, which were associated with decreased proliferation and type 2 cytokine productions by ILC2s. Furthermore, ILC2s from BQ123 treatment were found to be functionally impaired in response to an interleukin IL-33 challenged. And BQ123 treatment also affected the phosphorylation level of the extracellular signal-regulated kinase (ERK), as well as the level of GATA binding protein 3 (GATA3) in activated ILC2s. Interestingly, after BQ123 treatment, both mouse and human ILC2s in vitro exhibited decreased function and downregulation of ERK signaling and GATA3 stability. These observations imply that ETAR is an important regulator of ILC2 function and may be involved in ILC2-driven pulmonary inflammation. Therefore, blocking ETAR may be a promising therapeutic strategy for allergic airway inflammation.
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DOI：
10.1113/jp279077
发表时间：
2020-01
期刊：
The Journal of physiology
影响因子：
--
作者：
Craig JC;Broxterman RM;La Salle DT;Cerbie J;Ratchford SM;Gifford JR;Bunsawat K;Nelson AD;Bledsoe AD;Morgan DE;Wray DW;Richardson RS;Trinity JD
通讯作者：
Trinity JD
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：
16.6
作者：
Adams, Katrina L.;Riparini, Giulia;Gallo, Vittorio
通讯作者：
Gallo, Vittorio
影响因子：
7.3
作者：
Chen Z;Zhang X;Lv S;Xing Z;Shi M;Li X;Chen M;Zuo S;Tao Y;Xiao G;Liu J;He Y
通讯作者：
He Y
影响因子：
4.8
作者：
Bhowmick, N;Narayan, P;Puett, D
通讯作者：
Puett, D