IL-25/IL-33-responsive TH2 cells characterize nasal polyps with a default TH17 signature in nasal mucosa.
IL-25/IL-33-responsive TH2 cells characterize nasal polyps with a default TH17 signature in nasal mucosa.
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DOI：
10.1016/j.jaci.2015.10.019
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发表时间：
2016-05
期刊：
影响因子：
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通讯作者：
Till SJ
中科院分区：
文献类型：
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作者：
Lam EP;Kariyawasam HH;Rana BM;Durham SR;McKenzie AN;Powell N;Orban N;Lennartz-Walker M;Hopkins C;Ying S;Rimmer J;Lund VJ;Cousins DJ;Till SJ
西方国家慢性鼻窦炎伴鼻息肉病 (CRSwNP) 的特点是嗜酸性粒细胞增多、IgE 产生和 TH2 细胞因子表达。来自息肉的 2 型先天淋巴细胞响应 IL-25 和 IL-33 产生 IL-5 和 IL-13，尽管该轴与局部粘膜 T 细胞反应的相关性尚不清楚。我们试图研究 IL-25/IL-33 轴在 CRSwNP 患者局部粘膜 T 细胞反应中的作用。息肉组织和血液取自接受鼻息肉切除术的患者。对照鼻活检标本和血液取自健康志愿者。在短期外植体模型中培养组织。通过流式细胞术评估T细胞表面表型/细胞内细胞因子。 T 细胞受体可变 β 链分析采用immunoSEQ 测定进行。进行微阵列以进行基因表达分析。在鼻息肉组织中鉴定出表达 IL-25 受体 (IL-17RB) 的 TH2 效应细胞，但在健康鼻粘膜或周边未鉴定到。 IL-17RB+CD4+ 息肉衍生的 TH2 细胞共表达 ST2（IL-33 受体），并对 IL-25 和 IL-33 作出反应，增强 IL-5 和 IL-13 的产生。在 IL-17RB+CD4+ T 细胞内，在不同受试者中鉴定出几个相同的 T 细胞受体可变 β 链互补决定区 3 序列，表明克隆扩张是由共同抗原驱动的。在健康的鼻粘膜和息肉群体中观察到大量产生 IL-17 的 T 细胞，与外周血 T 细胞相比，TH17 相关基因的过度表达最多。 IL-25 和 IL-33 可以与 IL-17RB+ST2+ 息肉 T 细胞局部相互作用，增强 CRSwNP 患者的 TH2 反应。局部 TH17 反应可能对健康的鼻粘膜免疫稳态很重要。
Chronic rhinosinusitis with nasal polyposis (CRSwNP) in Western countries is characterized by eosinophilia, IgE production, and TH2 cytokine expression. Type 2 innate lymphoid cells from polyps produce IL-5 and IL-13 in response to IL-25 and IL-33, although the relevance of this axis to local mucosal T-cell responses is unknown. We sought to investigate the role of the IL-25/IL-33 axis in local mucosal T-cell responses in patients with CRSwNP. Polyp tissue and blood were obtained from patients undergoing nasal polypectomy. Control nasal biopsy specimens and blood were obtained from healthy volunteers. Tissue was cultured in a short-term explant model. T-cell surface phenotype/intracellular cytokines were assessed by means of flow cytometry. T-cell receptor variable β-chain analysis was performed with the immunoSEQ assay. Microarrays were performed for gene expression analysis. IL-25 receptor (IL-17RB)–expressing TH2 effector cells were identified in nasal polyp tissue but not the healthy nasal mucosa or periphery. IL-17RB+CD4+ polyp–derived TH2 cells coexpressed ST2 (IL-33 receptor) and responded to IL-25 and IL-33 with enhanced IL-5 and IL-13 production. Within IL-17RB+CD4+ T cells, several identical T-cell receptor variable β-chain complementarity-determining region 3 sequences were identified in different subjects, suggesting clonal expansion driven by a common antigen. Abundant IL-17–producing T cells were observed in both healthy nasal mucosal and polyp populations, with TH17-related genes the most overexpressed compared with peripheral blood T cells. IL-25 and IL-33 can interact locally with IL-17RB+ST2+ polyp T cells to augment TH2 responses in patients with CRSwNP. A local TH17 response might be important in healthy nasal mucosal immune homeostasis.