Malt1-Induced Cleavage of Regnase-1 in CD4⁺ Helper T Cells Regulates Immune Activation

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• 作者：Takuya Uehata¹ ; ⁴ ; Hidenori Iwasaki¹ ; ⁵ ; Alexis Vandenbon² ; Kazufumi Matsushita¹ ; ¹⁰ ; Eduardo Hernandez-Cuellar¹ ; Kanako Kuniyoshi¹ ; ³ ; Takashi Satoh¹ ; ³ ; Takashi Mino⁶ ; Yutaka Suzuki⁸ ; Daron M. Standley² ; Tohru Tsujimura⁹ ; Hiromi Rakugi⁴ ; Yoshitaka Isaka⁴ ; Osamu Takeuchi¹ ; ⁶ ; ⁷ ; Shizuo Akira¹ ; ³ ; ^{sakira@biken.osaka-u.ac.jp}
• 刊名：Cell
• 出版年：2013
• 出版时间：23 May, 2013
• 年：2013
• 卷：153
• 期：5
• 页码：1036-1049
• 全文大小：2809 K

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Summary

Regnase-1 (also known as Zc3h12a and MCPIP1) is an RNase that destabilizes a set of mRNAs, including Il6 and Il12b, through cleavage of their 3¡ä UTRs. Although Regnase-1 inactivation leads to development of an autoimmune disease characterized by T?cell activation and hyperimmunoglobulinemia in mice, the mechanism of Regnase-1-mediated immune regulation has remained unclear. We show that Regnase-1 is essential for preventing aberrant effector CD4⁺ T?cell generation cell autonomously. Moreover, in T?cells, Regnase-1 regulates the mRNAs of a set of genes, including c-Rel, Ox40, and Il2, through cleavage of their 3¡ä UTRs. Interestingly, T?cell receptor (TCR) stimulation leads to cleavage of Regnase-1 at R111 by Malt1/paracaspase, freeing T?cells from Regnase-1-mediated suppression. Furthermore, Malt1 protease activity is critical for controlling the mRNA stability of T?cell effector genes. Collectively, these results indicate that dynamic control of Regnase-1 expression in T?cells is critical for controlling T?cell activation.