Study On The Molecular Mechanisms Of The SNS Regulation Of The Immune System

Hua Gao (cell biology)Directed by Prof. Gang Pei It has been well established that the sympathetic nervous system (SNS) can regulate the immune system primarily by (2-adrenergic receptor ((2AR), an important G protein-coupled receptor (GPCR) in the immune system, and that nuclear factor-kappaB (NF-(B) plays a central role in innate and adaptive immunity. Here, we show that (-arrestin2, one of the major regulatory and signaling molecules in GPCR signal transduction, directly interacts with I(B( (inhibitor of NF-(B which retains NF-(B in the cytoplasm), and thus prevents phosphorylation and degradation of I(B(. Consequently, (-arrestin2, via its interaction with I(B(, can effectively modulate NF-(B activation and expression of NF-(B target genes. Moreover, stimulation of (2AR significantly enhances (-arrestin2-I(B( interaction and promotes (-arrestin2 stabilization of I(B(, indicating that (-arrestin2 mediates a cross-talk between (2AR and NF-(B signaling pathways. Taken together, the results from the current study may present one of underlying molecular mechanisms of the SNS regulation of the immune system.