Monhasery Niloufar, Moll Jens, Cuman Carly, Franke Manuel, Lamertz Larissa, Nitz Rebecca, Görg Boris, Häussinger Dieter, Lokau Juliane, Floss Doreen M, Piekorz Roland, Dimitriadis Eva, Garbers Christoph, Scheller Jürgen
Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany.
Centre for Reproductive Health, The Hudson Institute of Medical Research, Clayton, 3168 VIC, Australia; Department of Molecular and Translational Medicine, Monash University, Clayton, 3168 VIC, Australia.
Cell Rep. 2016 Jul 26;16(4):1067-1081. doi: 10.1016/j.celrep.2016.06.062. Epub 2016 Jul 14.
Interleukin (IL)-11 signaling is involved in various processes, including epithelial intestinal cell regeneration and embryo implantation. IL-11 signaling is initiated upon binding of IL-11 to IL-11R1 or IL-11R2, two IL-11α-receptor splice variants, and gp130. Here, we show that IL-11 signaling via IL-11R1/2:gp130 complexes occurs on both the apical and basolateral sides of polarized cells, whereas IL-6 signaling via IL-6R:gp130 complexes is restricted to the basolateral side. We show that basolaterally supplied IL-11 is transported and released to the apical extracellular space via transcytosis in an IL-11R1-dependent manner. By contrast, IL-6R and IL-11R2 do not promote transcytosis. In addition, we show that transcytosis of IL-11 is dependent on the intracellular domain of IL-11R1 and that synthetic transfer of the intracellular domain of IL-11R1 to IL-6R promotes transcytosis of IL-6. Our data define IL-11R as a cytokine receptor with transcytotic activity by which IL-11 and IL-6:soluble IL-6R complexes are transported across cellular barriers.
白细胞介素（IL）-11信号传导参与多种过程，包括肠上皮细胞再生和胚胎着床。IL-11与两种IL-11α受体剪接变体IL-11R1或IL-11R2以及gp130结合后启动IL-11信号传导。在此，我们发现通过IL-11R1/2:gp130复合物的IL-11信号传导在极化细胞的顶端和基底外侧均有发生，而通过IL-6R:gp130复合物的IL-6信号传导则局限于基底外侧。我们发现基底外侧提供的IL-11以依赖IL-11R1的方式通过转胞吞作用被运输并释放到顶端细胞外空间。相比之下，IL-6R和IL-11R2不促进转胞吞作用。此外，我们发现IL-11的转胞吞作用依赖于IL-11R1的细胞内结构域，并且将IL-11R1的细胞内结构域合成转移至IL-6R可促进IL-6的转胞吞作用。我们的数据将IL-11R定义为一种具有转胞吞活性的细胞因子受体，通过该受体IL-11和IL-6:可溶性IL-6R复合物可穿过细胞屏障进行运输。
