Aquaporin-9-expressing neutrophils are required for the establishment of contact hypersensitivity.
Aquaporin-9-expressing neutrophils are required for the establishment of contact hypersensitivity.
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DOI：
10.1038/srep15319
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发表时间：
2015-10-22
影响因子：
4.6
通讯作者：
Hara-Chikuma M
中科院分区：
文献类型：
--
作者：
Moniaga CS;Watanabe S;Honda T;Nielsen S;Hara-Chikuma M
水通道蛋白-9（AQP 9）是一种水/甘油通道蛋白，在包括中性粒细胞在内的多种免疫细胞中表达;然而，其在免疫应答中的作用仍然未知。在这里，我们显示AQP 9参与半抗原诱导的接触性超敏反应（CHS），作为皮肤过敏性接触性皮炎的小鼠模型，使用AQP 9敲除（AQP 9 −/−）小鼠。首先，与野生型（WT）小鼠相比，AQP 9 −/−小鼠对半抗原二硝基氟苯（DNFB）的CHS反应受损。致敏AQP 9 −/−引流淋巴结（dLN）细胞连续转移到WT受体中导致CHS反应降低，表明AQP 9 −/−小鼠的致敏性受损。其次，在致敏过程中向AQP 9 −/−小鼠给予WT中性粒细胞可挽救受损的CHS反应。半抗原应用后，神经元向dLN的募集因AQP 9缺陷而减弱。巧合的是，AQP 9 −/−中性粒细胞表现出降低的CC-趋化因子受体7（CCR 7）配体诱导的迁移效力，这归因于中性粒细胞对dLN的募集减弱。此外，我们发现，在AQP 9 −/−或嗜中性粒细胞缺失的小鼠中观察到的中性粒细胞缺乏减少了dLN细胞的IL-17 A产生，这可能是导致随后CHS反应期间T细胞活化的原因。综上所述，这些发现表明，AQP 9是通过调节中性粒细胞功能在皮肤获得性免疫应答期间发生致敏所必需的。
Aquaporin-9 (AQP9), a water/glycerol channel protein, is expressed in several immune cells including neutrophils; however, its role in immune response remains unknown. Here we show the involvement of AQP9 in hapten-induced contact hypersensitivity (CHS), as a murine model of skin allergic contact dermatitis, using AQP9 knockout (AQP9−/−) mice. First, the CHS response to hapten dinitrofluorobenzene (DNFB) was impaired in AQP9−/− mice compared with wild-type (WT) mice. Adoptive transfer of sensitized AQP9−/− draining lymph node (dLN) cells into WT recipients resulted in a reduced CHS response, indicating impaired sensitization in AQP9−/− mice. Second, administration of WT neutrophils into AQP9−/− mice during sensitization rescued the impaired CHS response. Neutrophil recruitment to dLNs upon hapten application was attenuated by AQP9 deficiency. Coincidentally, AQP9−/− neutrophils showed a reduced CC-chemokine receptor 7 (CCR7) ligand-induced migration efficacy, which was attributed to the attenuated recruitment of neutrophils to dLNs. Furthermore, we found that neutrophil deficiency, observed in AQP9−/− or neutrophil-depleted mice, decreased IL-17A production by dLN cells, which might be responsible for T cell activation during a subsequent CHS response. Taken together, these findings suggest that AQP9 is required for the development of sensitization during cutaneous acquired immune responses via regulating neutrophil function.