Mast cells, basophils, and eosinophils acquire constitutive IL-4 and IL-13 transcripts during lineage differentiation that are sufficient for rapid cytokine production
Mast cells, basophils, and eosinophils acquire constitutive IL-4 and IL-13 transcripts during lineage differentiation that are sufficient for rapid cytokine production
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DOI：
10.4049/jimmunol.174.2.1063
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发表时间：
2005-01-15
影响因子：
4.4
通讯作者：
Mohrs, M
中科院分区：
文献类型：
--
作者：
Gessner, A;Mohrs, K;Mohrs, M
肥大细胞、嗜碱性粒细胞和嗜酸性粒细胞是以其产生IL-4和IL-13的能力而区分的髓样细胞。然而，目前尚不清楚这种潜力是如何与这些子集的谱系分化。在本研究中，我们使用双顺反子IL-4报告（4get）小鼠直接可视化IL-4表达的非淋巴细胞在体外和体内的单细胞水平。我们的数据表明，两个IL-4等位基因的频繁表达启动和维持在个体发育过程中的IL-4 R α或Stat 6的独立机制。尽管在稳态条件下分化细胞中细胞因子转录物的组成性存在，但在不存在刺激的情况下细胞因子产生是不可检测的。此外，成熟肥大细胞、嗜碱性粒细胞和嗜酸性粒细胞也组成性表达IL-13。预先形成的IL-4和IL-13 mRNA都足以在刺激时快速产生细胞因子。我们的数据表明，肥大细胞，嗜碱性粒细胞和嗜酸性粒细胞的程序IL-4和IL-13的表达在个体发育早期。这些新的发现对过敏性和哮喘性疾病的预防和治疗干预具有重要意义。
Mast cells, basophils, and eosinophils are myeloid cells that are distinguished by their capability to produce IL-4 and IL-13. However, it is not clear how this potential is related to the lineage differentiation of these subsets. In the present study we used bicistronic IL-4 reporter (4get) mice to directly visualize IL-4 expression by nonlymphoid cells in vitro and in vivo at the single-cell level. Our data show that frequent expression of both Il4 alleles is initiated and maintained during ontogeny by an IL-4Ralpha- or Stat6-independent mechanism. Despite the constitutive presence of cytokine transcripts in differentiated cells under steady state conditions, cytokine production is not detectable in the absence of stimulation. Moreover, mature mast cells, basophils, and eosinophils also constitutively express IL-13. Both preformed IL-4 and IL-13 mRNAs are sufficient for rapid cytokine production upon stimulation. Our data show that mast cells, basophils and eosinophils are programmed for IL-4 and IL-13 expression early in ontogeny. These novel findings have important implications for the prevention and therapeutic intervention of allergic and asthmatic diseases.