The immune synapse, a highly organized structure formed at the interface between T lymphocytes and antigen-presenting cells (APCs), is essential for T cell activation and the adaptive immune response. It has been shown that this interface shares similarities with the primary cilium, a sensory organelle in eukaryotic cells, although the roles of ciliary proteins on the immune synapse remain elusive. Here, we find that inositol polyphosphate-5-phosphatase E (INPP5E), a cilium-enriched protein responsible for regulating phosphoinositide localization, is enriched at the immune synapse in Jurkat T-cells during superantigen-mediated conjugation or antibody-mediated crosslinking of TCR complexes, and forms a complex with CD3ζ, ZAP-70, and Lck. Silencing INPP5E in Jurkat T-cells impairs the polarized distribution of CD3ζ at the immune synapse and correlates with a failure of PI(4,5)P₂ clearance at the center of the synapse. Moreover, INPP5E silencing decreases proximal TCR signaling, including phosphorylation of CD3ζ and ZAP-70, and ultimately attenuates IL-2 secretion. Our results suggest that INPP5E is a new player in phosphoinositide manipulation at the synapse, controlling the TCR signaling cascade.

免疫突触是 T 淋巴细胞和抗原呈递细胞 (APC) 之间界面形成的高度组织化的结构，对于 T 细胞激活和适应性免疫反应至关重要。研究表明，该界面与初级纤毛（真核细胞中的一种感觉细胞器）有相似之处，尽管纤毛蛋白对免疫突触的作用仍然难以捉摸。在这里，我们发现肌醇多磷酸-5-磷酸酶 E (INPP5E) 是一种富含纤毛的蛋白质，负责调节磷酸肌醇定位，在超级抗原介导的缀合或抗体介导的 TCR 交联过程中，在 Jurkat T 细胞的免疫突触中富集复合物，并与 CD3ze、ZAP-70 和 Lck 形成复合物。Jurkat T 细胞中的 INPP5E 沉默会损害免疫突触处 CD3ze 的极化分布，并与突触中心PI(4,5)P _{2清除失败相关。}此外，INPP5E 沉默会降低近端 TCR 信号传导，包括 CD3ze 和 ZAP-70 的磷酸化，并最终减弱 IL-2 的分泌。我们的结果表明 INPP5E 是突触磷酸肌醇操纵的新参与者，控制 TCR 信号级联。