Regulatory T cells with reduced repressor capacities are extensively amplified in pulmonary sarcoid lesions and sustain granuloma formation
Regulatory T cells with reduced repressor capacities are extensively amplified in pulmonary sarcoid lesions and sustain granuloma formation
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DOI：
10.1016/j.clim.2011.03.015
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发表时间：
2011-07-01
影响因子：
8.6
通讯作者：
Abken, Hinrich
中科院分区：
文献类型：
--
作者：
Rappl, Gunter;Pabst, Stefan;Abken, Hinrich
结节病可演变为慢性疾病，伴有持续性肉芽肿和进行性纤维化。虽然无限制的炎症反应表明结节病病变的免疫控制受损，但与CD 4（+）CD 25（高）FoxP 3（+）调节性T细胞的大量浸润形成对比。我们在此发现，受影响的肺部病变中的Treg细胞主要来源于具有GARP（LRRC 32）阳性表型的活化的天然Treg细胞，但尽管IL-10和TGF-β 1水平高，但表现出抑制能力降低。相比之下，与年龄匹配的健康供体相比，血液Treg细胞的抑制能力并未受损。与同一患者的血液Treg细胞相比，肉芽肿病变中的Treg衍生细胞经历了由缩短的端粒指示的大量扩增。此外，病变Treg衍生的细胞分泌促炎细胞因子，包括IL-4，其通过成纤维细胞扩增和肥大细胞的活化维持肉芽肿形成，肥大细胞的活化通过膜结合的制瘤素M的表达指示。(C)2011 Elsevier Inc. All rights reserved.
Sarcoidosis can evolve into a chronic disease with persistent granulomas accompanied by progressive fibrosis. While an unlimited inflammatory response suggests an impaired immune control in sarcoid lesions, it stands in contrast to the massive infiltration with CD4(+)CD25(high)FoxP3(+) regulatory T cells. We here revealed that those Treg cells in affected lung lesions were mainly derived from activated natural Treg cells with GARP (LRRC32)-positive phenotype but exhibited reduced repressor capacities despite high IL-10 and TGF-beta 1 levels. The repressive capacity of blood Treg cells, in contrast, was not impaired compared to age-matched healthy donors. Treg derived cells in granuloma lesions have undergone extensive rounds of amplifications indicated by shortened telomeres compared to blood Treg cells of the same patient. Lesional Treg derived cells moreover secreted pro-inflammatory cytokines including IL-4 which sustains granuloma formation through fibroblast amplification and the activation of mast cells, the latter indicated by the expression of membrane-bound oncostatin M. (C) 2011 Elsevier Inc. All rights reserved.