Regulation of CARMA1 signaling and its role in immune homeostasis

我们证明了SH3-GUK在CARMA1中的相互作用是通过抗原受体激活NF-κB所必需的，通过调节CARMA1的多聚化，控制免疫突触中NF-κB信号体的形成。然而，在老年小鼠中，由于异常的Th2反应，缺乏这种相互作用，导致自身免疫样皮肤病变伴高ige。因此，CARMA1的SH3-GUK相互作用通过抗原受体在外周T细胞稳态中发挥重要作用。

We demonstrated that SH3-GUK interactions in CARMA1 is essential for NF-κB activation through antigen receptors by regulating multimerization CARMA1 that controls formation of NF-κB signalosome at immunological synapse. However, lack of this interaction in aged mice developed autoimmune-like skin lesions with hyper-IgE due to an aberrant Th2 response. Thus, SH3-GUK interactions of CARMA1 play an important role in peripheral T cell homeostasis through antigen receptors.