Induction of Prolonged Asthma Tolerance by IL-10-Differentiated Dendritic Cells: Differential Impact on Airway Hyperresponsiveness and the Th2 Immunoinflammatory Response
Induction of Prolonged Asthma Tolerance by IL-10-Differentiated Dendritic Cells: Differential Impact on Airway Hyperresponsiveness and the Th2 Immunoinflammatory Response
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DOI：
10.4049/jimmunol.1103286
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发表时间：
2012-07-01
影响因子：
4.4
通讯作者：
Gordon, John R.
中科院分区：
文献类型：
--
作者：
Nayyar, Aarti;Dawicki, Wojciech;Gordon, John R.
il -10分化的树突状细胞（DC10s）可以预防过敏原致敏并逆转已建立疾病小鼠的哮喘表型。然而，人们对这种容忍在什么时间范围内有效知之甚少。我们报道，在腹腔注射或经气管给OVA-哮喘小鼠1 × 10(6)个OVA-（但不含屋尘螨）DC10s后2周，气道高反应性（AHR）首先明显降低，而AHR在治疗后3至10周消失。13周时，AHR恢复到预处理水平，但可以通过DC10再处理再次逆转。在治疗后3周，单一DC10治疗对气道嗜酸性粒细胞和Th2细胞因子对召回OVA攻击的反应，以及对OVA特异性IgE/IgG1反应的影响是显著的，但此后逐渐增加，因此在8个月时，气道嗜酸性粒细胞和Th2对召回过敏原攻击的反应仍然与盐水治疗的哮喘小鼠相似，抑制了85-95%。四次双周DC10治疗，无论是经气管治疗还是腹腔治疗，在8周时将所有哮喘参数降低到接近背景，而s.c.d cdc10治疗不影响AHR，但确实降低了气道Th2反应（静脉注射DC10没有明显的影响）。在DC10治疗后的第12至21天，用雾化OVA （100 μ g/ml）反复刺激DC10治疗小鼠并没有逆转耐受性，但用吲哚胺-2,3-双加氧酶拮抗剂1-甲基色氨酸或中和抗il - 10r治疗部分逆转了耐受性（Th2细胞因子反应，但没有逆转AHR）。这些发现表明，在哮喘动物中，dc10诱导的Th2耐受性是长期存在的，但dc10通过不同的机制影响AHR与Th2免疫炎症参数。中国生物医学工程学报，2012,33(2):379 - 379。
IL-10-differentiated dendritic cells (DC10s) can prevent allergen sensitization and reverse the asthma phenotype in mice with established disease. However, little is known about the time-frames over which this tolerance is effective. We report that at 2 wk after i.p. or transtracheal delivery of 1 x 10(6) OVA-, but not house dust mite-presenting, DC10s to OVA-asthmatic mice, significant diminution of airway hyperresponsiveness (AHR) was first apparent, whereas AHR was abrogated between 3 and 10 wk posttreatment. At 13 wk, AHR returned to pretreatment levels but could again be reversed by DC10 retreatment. The impact of a single DC10 treatment on airway eosinophil and Th2 cytokine responses to recall OVA challenge, and on OVA-specific IgE/IgG1 responses, was substantial at 3 wk posttreatment, but progressively increased thereafter, such that at 8 mo, airway eosinophil and Th2 responses to recall allergen challenge remained similar to 85-95% suppressed relative to saline-treated asthmatic mice. Four biweekly DC10 treatments, whether transtracheal or i.p., reduced all asthma parameters to near background by 8 wk, whereas s.c. DC10 treatments did not affect AHR but did reduce the airway Th2 responses (i.v. DC10 had no discernible effects). Repeated challenge of the DC10-treated mice with aerosolized OVA (100 mu g/ml) did not reverse tolerance, but treatment with the indoleamine-2,3-dioxygenase antagonist 1-methyltryptophan or neutralizing anti-IL-10R from days 12 to 21 after DC10 therapy partially reversed tolerance (Th2 cytokine responses, but not AHR). These findings indicate that DC10-induced Th2 tolerance in asthmatic animals is long lived, but that DC10s employ distinct mechanisms to affect AHR versus Th2 immunoinflammatory parameters. The Journal of Immunology, 2012, 189: 72-79.