β-Arrestin 1 Modulates Functions Of Autoimmune T Cells From Primary Biliary Cirrhosis Patients

Primary biliary cirrhosis (PBC) is an autoimmune disease.β-arrestin 1 is a molecule involved in the intracellular signaling. It was reported thatβ-arrestin 1 is involved in the regulation of immune responses. This study is to explore the roles ofβ-arrestin 1 in the pathogenesis of PBC. By Fluoresences Quantative Polymerase Chain Reaction (FQ PCR) and western blot, we found that the levels ofβ-arrestin 1 mRNA and protein in PBMC from PBC patients werer higher markedly than those in control groups.Besides, the level ofβ-arrestin 1 mRNA was correlated to Mayo risk score positively. Moreover,β-arrestin1 promoted the proliferation of autoreactive T cell stimulated with autoantigen PDC-E2 peptides, augmenting interferon-γproduction, downregulating activities of muclear factorκB and AP-1. Futhermore,β-arrestin 1 promoted the expression of CD40L,LIGHT,IL-17 and IFN-γ,while inhibiting the expression of TRAIL,Apo2 and HDAC7A, which are all invoved in autoimmune responses. Further studies found thatβ-arrestin 1 modulated the acetylation of histone H4 in the promoter regions of these autoimmune correlated genes.In conclusion, these foundings indicated that ofβ-arrestin 1 regulated the functions of autoreactive T cells from PBC patients through epigenetics mechanisms, implying novel therapy strategy for PBC.