Project B01 - Mechanisms of CBM Signaling in regulatory T cells
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.
