严重哮喘ILC2s表现出经生物制剂修饰的增殖能力的增强
2023/05/25
摘要
背景：2型(T2)先天淋巴样细胞(ILC2s)参与气道炎症和哮喘疾病。我们假设从严重过敏性和嗜酸性哮喘患者中分离的ILC2s会表现出增强的T2炎症活性，这种活性会在mepolizumab和omalizumab治疗后改变。我们比较了健康无哮喘(HC)、非哮喘过敏(NAA)、轻度哮喘(MA)、重度过敏和嗜酸性哮喘(SA)受试者外周血(PB)分离ILC2的增殖能力、表型和IL-5和IL-13的分泌。然后，我们确定了6个月的mepolizumab或omalizumab治疗对SA受试者ILC2s生理的影响。
方法：在IL-2、IL-25、IL-33和胸腺基质淋巴生成素(TSLP)的作用下，将ILC2s分选培养14天。流式细胞术检测ILC2s的增殖、表型和功能。在使用美波珠单抗和奥玛珠单抗成功治疗SA患者后，重新评估ILC2s的反应。
结果：SA ILC2s的增殖能力、TSLP受体(TSLPR)、GATA3和NFATc1蛋白表达增加，IL-5和IL-13释放增加。ILC2s也能在刺激下释放IL-6。Mepolizumab治疗降低了ILC2s的增殖能力和TSLPR、GATA3和NFATc1的表达。mepolizumab和omalizumab均与ILC2s中IL-5和IL-13的释放减少相关，只有mepolizumab降低了IL-6的释放。
结论：严重过敏性和嗜酸性哮喘患者的ILC2s表现为活动性表型，表现为增殖增加，TSLPR、GATA3和NFATc1表达增加，IL-5、IL-13和IL-6释放增加。Mepolizumab降低了ILC2s激活标记物。
Severe asthma ILC2s demonstrate enhanced proliferation that is modified by biologics
B. Malik, N. W. Bartlett, J. W. Upham, K. S. Nichol, J. Harrington and P. A. B. Wark
BACKGROUND:Type 2 (T2) innate lymphoid cells (ILC2s) contribute to airway inflammation and disease in asthma. We hypothesize that ILC2s isolated from people with severe allergic and eosinophilic asthma would exhibit an enhanced T2 inflammatory activity that would be altered following treatment with mepolizumab and omalizumab. We compare peripheral blood (PB) isolated ILC2's proliferative capacity, IL-5 and IL-13 secretion and phenotype between healthy without asthma (HC), non-asthma allergic (NAA), mild asthma (MA) and severe allergic and eosinophilic asthma (SA) subjects. We then determined the impact of 6 months treatment with either mepolizumab or omalizumab on ILC2s physiology of SA subjects.
METHODS:ILC2s were sorted and cultured in the presence of IL-2, IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) for 14 days. ILC2s proliferation, phenotypes and functions were assessed using flowcytometry. The ILC2s response was then reassessed following clinically successful treatment of SA subjects with mepolizumab and omalizumab.
RESULTS: SA ILC2s demonstrated increased proliferative capacity, TSLP receptor (TSLPR), GATA3 and NFATc1 protein expressions and increased IL-5 and IL-13 release. ILC2s were also capable of releasing IL-6 in response to stimulation. Mepolizumab treatment reduced ILC2s proliferative capacity and expression of TSLPR, GATA3 and NFATc1. Both mepolizumab and omalizumab were associated with reduced ILC2s release of IL-5 and IL-13, only mepolizumab reduced IL-6.
CONCLUSIONS: ILC2s from severe allergic and eosinophilic asthma demonstrated an active phenotype typified by increased proliferation, TSLPR, GATA3 and NFATc1 expression and increased IL-5, IL-13 and IL-6 release. Mepolizumab reduced markers of ILC2s activation.
背景：2型(T2)先天淋巴样细胞(ILC2s)参与气道炎症和哮喘疾病。我们假设从严重过敏性和嗜酸性哮喘患者中分离的ILC2s会表现出增强的T2炎症活性，这种活性会在mepolizumab和omalizumab治疗后改变。我们比较了健康无哮喘(HC)、非哮喘过敏(NAA)、轻度哮喘(MA)、重度过敏和嗜酸性哮喘(SA)受试者外周血(PB)分离ILC2的增殖能力、表型和IL-5和IL-13的分泌。然后，我们确定了6个月的mepolizumab或omalizumab治疗对SA受试者ILC2s生理的影响。
方法：在IL-2、IL-25、IL-33和胸腺基质淋巴生成素(TSLP)的作用下，将ILC2s分选培养14天。流式细胞术检测ILC2s的增殖、表型和功能。在使用美波珠单抗和奥玛珠单抗成功治疗SA患者后，重新评估ILC2s的反应。
结果：SA ILC2s的增殖能力、TSLP受体(TSLPR)、GATA3和NFATc1蛋白表达增加，IL-5和IL-13释放增加。ILC2s也能在刺激下释放IL-6。Mepolizumab治疗降低了ILC2s的增殖能力和TSLPR、GATA3和NFATc1的表达。mepolizumab和omalizumab均与ILC2s中IL-5和IL-13的释放减少相关，只有mepolizumab降低了IL-6的释放。
结论：严重过敏性和嗜酸性哮喘患者的ILC2s表现为活动性表型，表现为增殖增加，TSLPR、GATA3和NFATc1表达增加，IL-5、IL-13和IL-6释放增加。Mepolizumab降低了ILC2s激活标记物。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Respirology, 2023 DOI: 10.1111/resp.14506）
（Respirology, 2023 DOI: 10.1111/resp.14506）
Severe asthma ILC2s demonstrate enhanced proliferation that is modified by biologics
B. Malik, N. W. Bartlett, J. W. Upham, K. S. Nichol, J. Harrington and P. A. B. Wark
BACKGROUND:Type 2 (T2) innate lymphoid cells (ILC2s) contribute to airway inflammation and disease in asthma. We hypothesize that ILC2s isolated from people with severe allergic and eosinophilic asthma would exhibit an enhanced T2 inflammatory activity that would be altered following treatment with mepolizumab and omalizumab. We compare peripheral blood (PB) isolated ILC2's proliferative capacity, IL-5 and IL-13 secretion and phenotype between healthy without asthma (HC), non-asthma allergic (NAA), mild asthma (MA) and severe allergic and eosinophilic asthma (SA) subjects. We then determined the impact of 6 months treatment with either mepolizumab or omalizumab on ILC2s physiology of SA subjects.
METHODS:ILC2s were sorted and cultured in the presence of IL-2, IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) for 14 days. ILC2s proliferation, phenotypes and functions were assessed using flowcytometry. The ILC2s response was then reassessed following clinically successful treatment of SA subjects with mepolizumab and omalizumab.
RESULTS: SA ILC2s demonstrated increased proliferative capacity, TSLP receptor (TSLPR), GATA3 and NFATc1 protein expressions and increased IL-5 and IL-13 release. ILC2s were also capable of releasing IL-6 in response to stimulation. Mepolizumab treatment reduced ILC2s proliferative capacity and expression of TSLPR, GATA3 and NFATc1. Both mepolizumab and omalizumab were associated with reduced ILC2s release of IL-5 and IL-13, only mepolizumab reduced IL-6.
CONCLUSIONS: ILC2s from severe allergic and eosinophilic asthma demonstrated an active phenotype typified by increased proliferation, TSLPR, GATA3 and NFATc1 expression and increased IL-5, IL-13 and IL-6 release. Mepolizumab reduced markers of ILC2s activation.
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Th2型炎症通过纤毛上皮细胞的功能的改变减少过敏性哮喘气道上皮中SARS-CoV-2的复制
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