J Immun：邵建忠等体液免疫调节机制研究获进展

近日，国际著名杂志The Journal of Immunology在线刊登了浙江大学生科院邵建忠教授实验室的最新研究成果“Essential Role of IL-4 and IL-4Rα Interaction in Adaptive Immunity of Zebrafish: Insight into the Origin of Th2-like Regulatory Mechanism in Ancient Vertebrates ”，文章中，研究者揭示了体液免疫调节机制的新进展。

T细胞起源进化是免疫生物学的重要命题，但目前尚缺乏深入研究和认识。IL-4介导的Th2型免疫应答是高等脊椎动物适应性体液免疫的重要调节机制，阐明该机制的演化规律对研究T细胞起源进化具有重要意义。

该研究采用斑马鱼实验模型证明了IL-4介导的Th2型免疫调节机制在早期脊椎动物鱼类中诞生，结合该课题组先前在鱼类中成功鉴定出Treg细胞，表明T细胞亚群分化出现于适应性免疫起源的初期。研究还发现了IL-4通过上调CD154/CD40共刺激信号促进Th2型免疫应答等分子机制。（生物谷Bioon.com）

doi:10.4049/​jimmunol.1102259
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Essential Role of IL-4 and IL-4Rα Interaction in Adaptive Immunity of Zebrafish: Insight into the Origin of Th2-like Regulatory Mechanism in Ancient Vertebrates

Lv-yun Zhu, Ping-ping Pan, Wei Fang, Jian-zhong Shao and Li-xin Xiang

The roles of IL-4 and IL-4Rα in Th2-mediated immunity have been well characterized in humans and other mammals. In contrast, few reports have been documented in ancient vertebrates. Several putative IL-4– and IL-4Rα–like molecules were identified recently from a few fish species, providing preliminary insight into the occurrence of Th2-type immunity in teleosts. However, functional determination still is required to address this hypothesis. To this end, these two molecules were characterized functionally in zebrafish (Danio rerio). Besides the identification of a full-length IL-4Rα molecule and an isoform lacking most of the cytoplasmic region as predicted previously, two novel alternatively spliced soluble variants with the extracellular domain only also were identified. Zebrafish IL-4Rα (DrIL-4Rα) shared overall conserved structural features of the IL-4Rα family. Immunofluorescence staining showed that DrIL-4Rα distributed on B cells. In vitro binding assays demonstrated that zebrafish IL-4 (DrIL-4) can bind specifically to DrIL-4Rα. In vivo administration of DrIL-4 significantly upregulated B cell proliferation and Ab production. These DrIL-4–elicited immune responses were downregulated by the administration of zebrafish soluble IL-4Rα or by DrIL-4Rα blockade using anti–DrIL-4Rα Abs. In addition, Th2-related cytokines or transcription factors were upregulated by DrIL-4. The DrIL-4–DrIL-4Rα interaction promoted CD40 expression on B cells and enhanced the CD154–CD40 costimulatory response, both of which are crucial for the initiation of Th2-type immunity. To our knowledge, this is the first report showing that a possible Th2-mediated regulatory mechanism may have appeared before the divergence of teleosts and mammals. These results add greater insight into the evolutionary history of adaptive immunity.