近日,，國(guó)際著名雜志The Journal of Immunology在線刊登了浙江大學(xué)生科院邵建忠教授實(shí)驗(yàn)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,，研究者揭示了體液免疫調(diào)節(jié)機(jī)制的新進(jìn)展,。
T細(xì)胞起源進(jìn)化是免疫生物學(xué)的重要命題,，但目前尚缺乏深入研究和認(rèn)識(shí)。IL-4介導(dǎo)的Th2型免疫應(yīng)答是高等脊椎動(dòng)物適應(yīng)性體液免疫的重要調(diào)節(jié)機(jī)制,，闡明該機(jī)制的演化規(guī)律對(duì)研究T細(xì)胞起源進(jìn)化具有重要意義,。
該研究采用斑馬魚(yú)實(shí)驗(yàn)?zāi)Ｐ妥C明了IL-4介導(dǎo)的Th2型免疫調(diào)節(jié)機(jī)制在早期脊椎動(dòng)物魚(yú)類中誕生，結(jié)合該課題組先前在魚(yú)類中成功鑒定出Treg細(xì)胞,，表明T細(xì)胞亞群分化出現(xiàn)于適應(yīng)性免疫起源的初期,。研究還發(fā)現(xiàn)了IL-4通過(guò)上調(diào)CD154/CD40共刺激信號(hào)促進(jìn)Th2型免疫應(yīng)答等分子機(jī)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.
