Mechanismen der CBM-Signalübertragung in regulatorischen T-Zellen (B01)

我们先前的工作已经证明，由CARD 11、BCL 10和MALT 1组成的信号传导复合物（CBM复合物）不仅控制TCR诱导的NF-κB信号传导，而且对于Treg发育以及在稳态条件下静息T细胞转化为效应T细胞（r/eT细胞）也是必不可少的。然而，在炎症环境中，细胞因子可以绕过CBM对NF-κ B介导的分化步骤的要求。然而，CBM信号传导对于Treg细胞的抑制功能是绝对关键的，并且这种活性通过MALT 1亚基的蛋白水解功能非冗余地介导。在该项目中，我们希望探索和定义已建立的Tcls中的MALT 1介导的机制，该机制在CBM复合物水平上分离终末Treg分化和抑制途径，为在免疫介导的疾病中操纵这些途径提供基础。

Our previous work has demonstrated that signaling complexes composed of CARD11, BCL10 and MALT1 (CBM complexes) not only control TCR-induced NF-κB signaling, but are also essential for Treg development as well as for the conversion of resting to effector Tregs (r/eTregs) under homeostatic conditions. However, in inflammatory milieus, cytokines can bypass the CBM requirement for this NF-κB-mediated differentiation step. Nevertheless, CBM signaling is absolutely critical for suppressive function of Treg cells and this activity is non-redundantly mediated via a proteolytic function of the MALT1 subunit. Within this project, we want to explore and define the MALT1-mediated mechanisms within established Tregs that segregate the terminal Treg differentiation and suppressive pathways at the CBM complex level to provide a basis for the manipulation of these pathways in immune-mediated diseases.