Deficiency of β-Arrestin 2 in Dendritic Cells Contributes to Autoimmune Diseases

Abstract

Abstract Altered migration and immune responses of dendritic cells (DCs) lead to inflammatory and autoimmune diseases. Our studies demonstrated that β-arrestin 2 deficiency promoted migration and cytokine production of mouse bone marrow–derived DCs. We further found that β-arrestin 2 directly interacted with Zbtb46, a DC-specific transcription factor. What’s more, our results suggested that the interaction between β-arrestin 2 and Zbtb46 might negatively regulate DC migration. Using RNA sequencing, we indicated that genes CD74, NR4A1, and ZFP36 might be the target genes regulated by the interaction between β-arrestin 2 and Zbtb46. Mice with selective deficiency of β-arrestin 2 in DCs developed severer experimental autoimmune encephalomyelitis with more DC infiltration in the CNS and increased IL-6 in serum. In the systemic lupus erythematosus mice model, Arrb2fl/fl Itgax-cre+ mice were prone to exacerbation of lupus nephritis with a higher level of IL-6 and DC accumulation. Taken together, our study identified β-arrestin 2 as a new regulator of DC migration and immune properties, providing new insights into the mechanisms underlying the development of autoimmune disease.