Skewed Lung CCR4 to CCR6 CD4(+) T Cell Ratio in Idiopathic Pulmonary Fibrosis Is Associated with Pulmonary Function.
Skewed Lung CCR4 to CCR6 CD4(+) T Cell Ratio in Idiopathic Pulmonary Fibrosis Is Associated with Pulmonary Function.
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DOI：
10.3389/fimmu.2016.00516
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发表时间：
2016
影响因子：
7.3
通讯作者：
Sperling AI
中科院分区：
文献类型：
--
作者：
Adegunsoye A;Hrusch CL;Bonham CA;Jaffery MR;Blaine KM;Sullivan M;Churpek MM;Strek ME;Noth I;Sperling AI
特发性肺纤维化（IPF）是一种进行性、致死性肺部疾病。虽然已经表明T细胞可能有助于IPF发病机制，但这些研究主要集中在肺结节外的T细胞。因此，T细胞在患病肺组织中的作用仍不清楚。确定特异性CD4+ T细胞亚群在IPF患者肺组织中的表达是否存在差异。在肺移植时从IPF患者以及年龄和性别匹配的无已知肺部疾病的器官供体获得的肺组织中测量CD4+ T细胞亚群。通过CCR4、CCR6和CXCR3趋化因子受体的表面表达鉴定亚组。CD4+ T细胞亚群与移植前获得的肺功能测量值相关。与对照组相比，IPF患者的肺CD4+ T细胞比例较高，CCR4+ CD4+ T细胞比例较高，CCR6+ CD4+ T细胞比例较低。IPF肺组织中CCR4+ CD4+ T细胞的增加不是由于TcR增加。有趣的是，CCR4+细胞与CCR6+细胞比率的增加与更好的肺功能显著相关。我们的研究结果提示了一种新的范式，即并非IPF肺部的所有T细胞浸润都是有害的，相反，专门的亚群实际上可能是保护性的。因此，增加招募保护性T细胞的趋化因子，同时阻断招募有害T细胞的趋化因子，可能构成一种治疗特发性肺纤维化的新方法。
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease. While it has been suggested that T cells may contribute to IPF pathogenesis, these studies have focused primarily on T cells outside of the pulmonary interstitium. Thus, the role of T cells in the diseased lung tissue remains unclear. To identify whether specific CD4+ T cell subsets are differentially represented in lung tissue from patients with IPF. CD4+ T cell subsets were measured in lung tissue obtained from patients with IPF at the time of lung transplantation, and from age- and gender-matched organ donors with no known lung disease. Subsets were identified by their surface expression of CCR4, CCR6, and CXCR3 chemokine receptors. CD4+ T cell subsets were correlated with measurements of lung function obtained prior to transplantation. Compared to controls, IPF patients had a higher proportion of lung CD4+ T cells, a higher proportion of CCR4+ CD4+ T cells, and a lower proportion of CCR6+ CD4+ T cells. The increase in CCR4+ CD4+ T cells in IPF lung tissue was not due to increased Tregs. Intriguingly, the increase in the ratio of CCR4+ cells to CCR6+ cells correlated significantly with better lung function. Our findings suggest a new paradigm that not all T cell infiltrates in IPF lungs are detrimental, but instead, specialized subsets may actually be protective. Thus, augmentation of the chemokines that recruit protective T cells, while blocking chemokines that recruit detrimental T cells, may constitute a novel approach to IPF therapy.
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影响因子：
3.7
作者：
Gilani SR;Vuga LJ;Lindell KO;Gibson KF;Xue J;Kaminski N;Valentine VG;Lindsay EK;George MP;Steele C;Duncan SR
通讯作者：
Duncan SR
影响因子：
5.8
作者：
Hostettler KE;Zhong J;Papakonstantinou E;Karakiulakis G;Tamm M;Seidel P;Sun Q;Mandal J;Lardinois D;Lambers C;Roth M
通讯作者：
Roth M
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
6
作者：
Christensen, PJ;Goodman, RE;Toews, GB
通讯作者：
Toews, GB
DOI：
10.1165/rcmb.2014-0150oc
发表时间：
2015-09-01
影响因子：
6.4
作者：
Khalil, Wajahat;Xia, Hong;Henke, Craig A.
通讯作者：
Henke, Craig A.