Interleukin-11 receptor is an alternative α-receptor for interleukin-6 and the chimeric cytokine IC7.

Hendrik T Weitz, Julia Ettich, Puyan Rafii, Christoph Wittich, Laura Schultz, Nils C Frank, Denise Heise, Matthias Krusche, Juliane Lokau, Christoph Garbers, Kristina Behnke, Doreen M Floss, Harald Kolmar, Jens M Moll, Jürgen Scheller
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Abstract

The cytokine interleukin 6 (IL-6) signals via the IL-6 α-receptor (IL-6Rα or IL-6R) in complex with the gp130 β-receptor. Cell type restricted expression of the IL-6R limits the action of IL-6 mainly to hepatocytes and some immune cells. Here, we show that IL-6 also binds to the IL-11 α receptor (IL-11Rα or IL-11R) and induces signaling via IL-11R:gp130 complexes, albeit with a lower affinity compared to IL-11. Antagonistic antibodies directed against IL-11R, but not IL-6R, inhibit IL-6 signaling via IL-11R:gp130 receptor complexes. Notably, IL-11 did not cross-react with IL-6R. IL-11R has also been identified as an alternative α receptor for the CNTF/IL-6-derived chimeric cytokine IC7, which has recently been shown to induce weight loss in mice. Accordingly, the effects of therapeutic monoclonal antibodies against IL-6 or IL-6R, which both block IL-6 signaling, may be slightly different. These findings provide new insights into IL-6 signaling and therefore offer new potential therapeutic intervention options in the future.

白细胞介素-11 受体是白细胞介素-6 和嵌合细胞因子 IC7 的另一种 α 受体。
细胞因子白细胞介素 6(IL-6)通过 IL-6 α-受体(IL-6Rα 或 IL-6R)与 gp130 β-受体复合物发出信号。IL-6R 的表达受细胞类型的限制,IL-6 的作用主要局限于肝细胞和一些免疫细胞。在这里,我们发现 IL-6 也能与 IL-11 α 受体(IL-11Rα 或 IL-11R)结合,并通过 IL-11R:gp130 复合物诱导信号传导,尽管其亲和力低于 IL-11。针对 IL-11R 而非 IL-6R 的拮抗抗体能抑制 IL-6 通过 IL-11R:gp130 受体复合物发出信号。值得注意的是,IL-11 与 IL-6R 没有交叉反应。IL-11R还被确定为CNTF/IL-6衍生的嵌合细胞因子IC7的替代α受体,而IC7最近被证明可诱导小鼠体重减轻。因此,针对IL-6或IL-6R的治疗性单克隆抗体(两者都能阻断IL-6信号传导)的效果可能略有不同。这些发现提供了有关IL-6信号传导的新见解,因此为未来提供了新的潜在治疗干预方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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