Diametric Role of the Latency-Associated Protein Acr1 of in Modulating the Functionality of Pre- and Post-maturational Stages of Dendritic Cells.

It is instrumental for the to persist within its host in dormancy. represses most of its metabolic machinery during latency, but upregulates the expression of latency-associated protein alpha-crystallin protein (Acr1). Therefore, it is imperative to understand how throughout dormancy, employs Acr1 to regulate the host immunity. This study reveals that Acr1 exhibits divergent effect on the pre- and post-maturation stages of dendritic cells (DCs). In the current study, we demonstrate that early encounter of bone marrow cells with Acr1 while differentiating into DCs (AcrDC), leads to impairment in their maturation. In contrast, when exposed to Acr1 after maturation (AcrDC), DCs show augmentation in their activity, secretion of TNF-α, IL-12, IL-6, and activation of T cells. Additionally, AcrDC promoted the polarization of naïve CD4 T cells to Th1 cells and Th17 cells and restricted the intracellular growth of . Furthermore, these DCs upregulated the expression of CCR7 and exhibited enhanced migratory capabilities. The discrete impact of Acr1 on DCs is mediated through a mechanism involving STAT-1, SOCS-3, ERK, TLR-4, and NF-κB signaling pathways. This study reveals the unprecedented role of Acr1 in distinctly modulating the function of DCs at different stages of maturation.