Therapeutical measures to control airway tolerance in asthma and lung cancer.
Therapeutical measures to control airway tolerance in asthma and lung cancer.
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DOI：
10.3389/fimmu.2012.00216
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发表时间：
2012
影响因子：
7.3
通讯作者：
Finotto S
中科院分区：
文献类型：
--
作者：
Andreev K;Graser A;Maier A;Mousset S;Finotto S
呼吸道耐受是一种特殊的免疫监视，由肺细胞激活，以处理和区分无害和致病的吸入剂。然而，这种区别并不总是发生。气道耐受性对于避免过敏性疾病如哮喘的发展是必要的，哮喘由气道中Th 2和Th 17细胞的病理性扩增主导。相比之下，肿瘤细胞在其微环境中诱导致耐受性因子以逃避T细胞介导的抗肿瘤免疫应答。本文就TGF-β、IL-10和IL-17 A等细胞因子在肺抗原免疫应答中的作用及其与过敏性哮喘和肺癌的关系作一综述。审查的目的是评估治疗干预在哪些方面可行，哪些方面可能失败。这些细胞因子的多功能作用进一步使其用作治疗靶标的时机和浓度的决定复杂化。事实上，TGF-β在早期肿瘤发生中具有抑制活性，但在疾病的后期阶段可能成为肿瘤促进剂。这种双重行为有时是由于TGF-β的细胞靶标的变化以及诱导的⑴-TGF 3的扩增。类似地，已发现IL-17 A引发促肿瘤以及抗肿瘤特性。因此，这种促炎细胞因子诱导干扰Treg发育的IL-6的产生。然而，IL-17 A可以促进肿瘤生长与IL-6依赖性激活Stat 3。因此，了解气道耐受的机制有助于改善过敏性哮喘和肺癌的治疗。因此，哮喘治疗旨在诱导和维持对吸入性变应原的耐受性，而针对肺癌的治疗试图抑制肿瘤周围的致耐受性反应。
Airway tolerance is a specialized immunological surveillance which is activated by the cells of the lung to deal with and distinguish between innocuous and pathogenic inhalants. However, this distinction does not always occur. Airway tolerance is necessary to avoid the development of allergic disorders, such as asthma, which is dominated by a pathological expansion of Th2 and Th17 cells in the airways. By contrast, tumor cells induce tolerogenic factors in their microenvironment to evade T-cell mediated anti-tumor-immune responses. This review updates current understandings on the effect of the cytokines TGF-β, IL-10, and IL-17A on the lung immune responses to antigen, and analyzes their involvement in allergic asthma and lung cancer. The aim of the review is to evaluate where therapeutic intervention may be feasible and where it might fail. The multifunctional role of these cytokines further complicates the decision on the timing and concentration for their use as therapeutical targets. In fact, TGF-β has suppressive activity in early tumorigenesis, but may become tumor-promoting in the later stages of the disease. This dual behavior is sometimes due to changes in the cellular target of TGF-β, and to the expansion of the induced (i)-Tregs. Similarly, IL-17A has been found to elicit pro- as well as anti-tumor properties. Thus, this pro-inflammatory cytokine induces the production of IL-6 which interferes with Treg development. Yet IL-17A could promote tumor growth in conjunction with IL-6-dependent activation of Stat3. Thus, understanding the mechanisms of airway tolerance could help to improve the therapy to both, allergic asthma and lung cancer. Hereby, asthma therapy aims to induce and maintain tolerance to inhaled allergens and therapy against lung cancer tries to inhibit the tolerogenic response surrounding the tumor.
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DOI：
10.3410/b1-5
发表时间：
2009-01-21
期刊：
F1000 biology reports
影响因子：
--
作者：
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通讯作者：
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影响因子：
4.4
作者：
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影响因子：
50.5
作者：
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通讯作者：
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影响因子：
82.9
作者：
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通讯作者：
Luster, AD
DOI：
10.1165/rcmb.4832
发表时间：
2003-01-01
影响因子：
6.4
作者：
Hellings, PW;Kasran, A;Ceuppens, JL
通讯作者：
Ceuppens, JL