Patients with cystic fibrosis have inducible IL-17+IL-22+ memory cells in lung draining lymph nodes.
Patients with cystic fibrosis have inducible IL-17+IL-22+ memory cells in lung draining lymph nodes.
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DOI：
10.1016/j.jaci.2012.05.036
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发表时间：
2013-04
影响因子：
14.2
通讯作者：
Kolls, Jay K.
中科院分区：
文献类型：
--
作者：
Chan, Yvonne R.;Chen, Kong;Duncan, Steven R.;Lathrop, Kira L.;Latoche, Joseph D.;Logar, Alison J.;Pociask, Derek A.;Wahlberg, Brendon J.;Ray, Prabir;Ray, Anuradha;Pilewski, Joseph M.;Kolls, Jay K.
关键词：
白细胞介素 (IL)-17 是 T 辅助细胞分化途径 Th17 的重要细胞因子特征。这种 T 细胞亚群在动物模型中介导自身免疫性疾病或抗菌免疫方面至关重要，但其在人类疾病中的存在和作用仍有待完全表征。我们着手确定囊性纤维化 (CF) 中 Th17 细胞的频率，囊性纤维化是一种已知病原体反复感染的疾病。收集接受移植的患者或器官捐献者（CF = 18，非 CF，非支气管扩张 = 10）的外植肺。处理肺门淋巴结和实质肺组织。我们通过免疫荧光和实时定量 PCR 检查了它们的 Th17 特征。分离 T 细胞并用来自铜绿假单胞菌和曲霉属的抗原进行刺激。使用细胞因子谱和流式细胞术染色来评估这些细胞对抗原刺激的反应性。与非 CF 对照相比，我们发现 CF 中存在强烈的 IL-17 表型。在该组织中，我们发现了病原体抗原反应性 CD4+IL17+ 细胞。存在双阳性IL-17+IL-22+细胞，且IL-22+群体具有较高比例的记忆特征。与匹配的肺实质相比，引流淋巴结中的抗原特异性 Th17 反应更强。在 CF 肺中观察到具有记忆细胞特征的 Th17(22) 的诱导增殖。这些个体亚群的功能需要对其发育进行进一步研究。 T 细胞可能不是 IL-17 和 IL-22 的唯一产生者，这需要进一步表征。
Interleukin (IL)-17 is an important cytokine signature of a T helper differentiation pathway, Th17. This T cell subset is crucial in mediating autoimmune disease or antimicrobial immunity in animal models, but its presence and role in human disease remains to be completely characterized. We set out to determine the frequency of Th17 cells in cystic fibrosis (CF), a disease in which there is recurrent infection with known pathogens. Explanted lungs from patients undergoing transplant or organ donors (CF = 18, non-CF, non-bronchiectatic = 10) were collected. Hilar nodes and parenchymal lung tissue were processed. We examined them for Th17 signature by immunofluorescence and quantitative real time PCR. T cells were isolated and stimulated with antigens from Pseudomonas aeruginosa and Aspergillus. Cytokine profiles and staining by flow cytometry were used to assess the reactivity of these cells to antigen stimulation. We found a strong IL-17 phenotype in CF compared to non-CF controls. Within this tissue, we found pathogen-antigen-responsive CD4+IL17+ cells. There were double positive IL-17+IL-22+ cells and the IL-22+ population had higher proportions of memory characteristics. Antigen-specific Th17 responses were stronger in the draining lymph nodes compared to matched parenchymal lung. Inducible proliferation of Th17(22) with memory cell characteristics is seen in CF lung. The function of these individual subpopulations will require further study regarding their development. T-cells are likely not the exclusive producers of IL-17 and IL-22 and this will require further characterization.
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影响因子：
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