The polarization of leukocytes toward chemoattractants is essential for the directed migration (chemotaxis) of leukocytes. How leukocytes acquire polarity after encountering chemical gradients is not well understood. We found here that leukocyte polarity was generated by TIPE2 (TNFAIP8L2), a transfer protein for phosphoinositide second messengers. TIPE2 functioned as a local enhancer of phosphoinositide-dependent signaling and cytoskeleton remodeling, which promoted leading-edge formation. Conversely, TIPE2 acted as an inhibitor of the GTPase Rac, which promoted trailing-edge polarization. Consequently, TIPE2-deficient leukocytes were defective in polarization and chemotaxis, and TIPE2-deficient mice were resistant to leukocyte-mediated neural inflammation. Thus, the leukocyte polarizer is a dual-role phosphoinositide-transfer protein and represents a potential therapeutic target for the treatment of inflammatory diseases.

中文翻译：

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磷酸肌醇转移蛋白TIPE2对白细胞极化和迁移的指导。

白细胞向趋化剂的极化对于白细胞的定向迁移（趋化性）是必不可少的。白细胞在遇到化学梯度后如何获得极性尚不完全清楚。我们在这里发现白细胞极性是由TIPE2（TNFAIP8L2）产生的，TIPE2是磷酸肌醇第二信使的转移蛋白。TIPE2充当磷酸肌醇依赖性信号传导和细胞骨架重塑的局部增强剂，从而促进了前沿形成。相反，TIPE2充当GTPase Rac的抑制剂，可促进后缘极化。因此，缺乏TIPE2的白细胞在极化和趋化性方面有缺陷，而缺乏TIPE2的小鼠对白细胞介导的神经炎症有抵抗力。因此，