Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2.
Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2.
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DOI：
10.4049/immunohorizons.2300039
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发表时间：
2023-06-01
期刊：
影响因子：
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通讯作者：
Robinson RT
中科院分区：
文献类型：
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作者：
Mahfooz NS;Merling MR;Claeys TA;Dowling JW;Forero A;Robinson RT
IL-35是一种免疫抑制细胞因子，在癌症、自身免疫和感染性疾病中发挥作用。在传统的IL-35生物学模型中，该细胞因子的p35和Ebi3结构域分别与调节性T细胞和调节性B细胞表面的IL-12Rβ2和gp130相互作用，触发它们对Th细胞活性的抑制。在这里，我们使用人IL-12生物活性报告细胞系、蛋白质结合试验和原代人Th细胞来证明IL-35抑制Th细胞活性的另一种机制，其中IL-35直接抑制IL-12与其表面受体IL-12Rβ2的关联以及下游IL-12依赖性活性。IL-12与表面受体IL-12Rβ1的结合不受IL-35的影响。这些数据表明，除了通过调节性T细胞和调节性B细胞起作用外，人IL-35还可以直接抑制IL-12的生物活性及其与IL-12Rβ2的相互作用。
IL-35 is an immunosuppressive cytokine with roles in cancer, autoimmunity, and infectious disease. In the conventional model of IL-35 biology, the p35 and Ebi3 domains of this cytokine interact with IL-12Rβ2 and gp130, respectively, on the cell surface of regulatory T and regulatory B cells, triggering their suppression of Th cell activity. Here we use a human IL-12 bioactivity reporter cell line, protein binding assays, and primary human Th cells to demonstrate an additional mechanism by which IL-35 suppresses Th cell activity, wherein IL-35 directly inhibits the association of IL-12 with its surface receptor IL-12Rβ2 and downstream IL-12–dependent activities. IL-12 binding to the surface receptor IL-12Rβ1 was unaffected by IL-35. These data demonstrate that in addition to acting via regulatory T and regulatory B cells, human IL-35 can also directly suppress IL-12 bioactivity and its interaction with IL-12Rβ2.