Roles of interleukin-1 family cytokines and their receptors in neuronal synapse formation

白细胞介素-1受体辅助蛋白（IL-1RAcP）是介导白细胞介素-1家族细胞因子免疫和炎症反应的受体复合物的重要组成部分。通过成纤维细胞-神经元混合培养实验，我们发现IL-1RAcP在培养的皮质神经元中具有强大的突触形成活性。IL-1RAcP通过胞外结构域与蛋白酪氨酸磷酸酶（PTP）相互作用。PTP δ基因敲除小鼠皮层神经元中IL-1RAcP的突触生成活性降低。相应的，PTP δ需要IL-1RAcP来诱导突触后分化。此外，IL-1RAcP敲除小鼠皮质和海马锥体神经元的脊柱密度降低。这些结果表明，IL-1RAcP在脑内作为跨突触细胞粘附分子，通过PTP δ组织突触形成。

Interleukin-1 receptor accessory protein (IL-1RAcP) is the essential component of receptor complexes mediating immune and inflammatory responses to interleukin-1 family cytokines. Using a fibroblast-neuron mixed culture assay, we found robust synaptogenic activity of IL-1RAcP in cultured cortical neurons. IL-1RAcP interacted with protein tyrosine phosphatase (PTP) delta through the extracellular domain. The synaptogenic activity of IL-1RAcP was diminished in cortical neurons from PTP delta knockout mice. Correspondingly, PTP delta required IL-1RAcP to induce postsynaptic differentiation. Furthermore, the spine densities of cortical and hippocampal pyramidal neurons were reduced in IL-1RAcP knockout mice. These results suggest that IL-1RAcP functions as trans-synaptic cell adhesion molecules in the brain and organize synapse formation through PTP delta .