CD45RB Ligation inhibits allergic pulmonary inflammation by inducing CTLA4 transcription
CD45RB Ligation inhibits allergic pulmonary inflammation by inducing CTLA4 transcription
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DOI：
10.4049/jimmunol.179.6.4212
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发表时间：
2007-09-15
影响因子：
4.4
通讯作者：
Finn, Patricia W.
中科院分区：
文献类型：
--
作者：
Jen, Kai Yu;Campo, Monica;Finn, Patricia W.
CD 45是一种在有核造血细胞上表达的I型跨膜蛋白酪氨酸磷酸酶，主要参与T细胞活化。CD 45 RB同种型的连接与移植耐受相关。最近的哮喘基因分型分析表明与CD 45剪接相关。在这项研究中，我们在过敏性哮喘的小鼠模型中施用抗CD 45 RB mAb（aCD 45），发现CD 45 RB连接降低过敏反应。aCD 45降低变应原诱导的肺嗜酸性粒细胞增多症、支气管肺泡灌洗IL-13、IgE和气道反应。此外，aCD 45增加CTLA 4的表达，CTLA 4是T细胞活化的负调节剂。此外，当CTLA 4被抑制时，CD 45 RB信号不再减少过敏性炎症。这些数据支持CTLA 4在CD 45 RB介导的过敏性炎症抑制中的作用。用aCD 45刺激的T细胞和脾细胞表现出增加的CTLA 4水平，并且CTLA 4启动子基因构建体的分析鉴定了相对于转录起始位点位于-335至-62 bp的CD 45 RB诱导型调控区。总之，这些发现表明，CD 45 RB信号介导的过敏性炎症的调制中的新的作用，由T细胞通过诱导CTLA 4转录编排。
CD45, a type I transmembrane protein tyrosine phosphatase expressed on nucleated hemopoietic cells, is prominently involved in T cell activation. Ligation of CD45RB isoforms has been associated with transplant tolerance. A recent genotyping analysis of asthma indicates a correlation with CD45 splicing. In this study, we administered an anti-CD45RB mAb (aCD45) in a murine model of allergic asthma and found that CD45RB ligation decreases allergic responses. aCD45 decreases allergen-induced pulmonary eosinophilia, bronchoalveolar lavage IL-13, IgE, and airway responses. Also, aCD45 increases the expression of CTLA4, a negative regulator of T cell activation. Furthermore, CD45RB signals no longer decrease allergic inflammation when CTLA4 is inhibited. These data support a role for CTLA4 in CD45RB-mediated inhibition of allergic inflammation. T cells and splenocytes stimulated with aCD45 exhibited increased CTLA4 levels, and analysis of CTLA4 promoter gene constructs identified a CD45RB-inducible regulatory region localized from -335 to -62 bp relative to the transcription start site. Together, these findings suggest that CD45RB signals mediate a novel role in the modulation of allergic inflammation, orchestrated by T cells through induction of CTLA4 transcription.