Enpp2 Expression by Dendritic Cells Is a Key Regulator in Migration

Abstract

Enpp2 is an enzyme that catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which exhibits a wide variety of biological functions. Here, we examined the biological effects of Enpp2 on dendritic cells (DCs), which are specialized antigen-presenting cells (APCs) characterized by their ability to migrate into secondary lymphoid organs and activate naïve T-cells. DCs were generated from bone marrow progenitors obtained from C57BL/6 mice. Enpp2 levels in DCs were regulated using small interfering (si)RNA or recombinant Enpp2. Expression of Enpp2 in LPS-stimulated mature (m)DCs was high, however, knocking down Enpp2 inhibited mDC function. In addition, the migratory capacity of mDCs increased after treatment with rmEnpp2; this phenomenon was mediated via the RhoA-mediated signaling pathway. Enpp2-treated mDCs showed a markedly increased capacity to migrate to lymph nodes in vivo. These findings strongly suggest that Enpp2 is necessary for mDC migration capacity, thereby increasing our understanding of DC biology. We postulate that regulating Enpp2 improves DC migration to lymph nodes, thus improving the effectiveness of cancer vaccines based on DC.

Effects of Xinjiang wild cherry plum (Prunus divaricata Ledeb) anthocyanin-rich extract on the plasma metabolome of atherosclerotic apoE-deficient mice fed a high-fat diet

“…ENPP2 is an adipose-derived, secreted enzyme that catalyzes lysophosphatidylcholine to form lysophosphatidic acid, a biological molecule possessing various biological effects. ENPP2 has been reported implication in multiple physiopathological processes, such as dendritic cell migration ( 37 ), adipose tissue expansion, and insulin resistance ( 38 ). AGPAT1, as an intermediate enzyme in the pathway for the biosynthesis of glycerophospholipids, catalyzes the acylation of lysophosphatidic acid to produce phosphatidic acid ( 39 ).…”

Dendritic Cell-Based Immunotherapy: The Importance of Dendritic Cell Migration

“…Furthermore, IL-10 and tumor growth factor (TGF)- β 1 promote cellular adhesion while inhibiting DC migration to dLN [ 77 ]. Ectonucleotide pyrophosphatase/phosphodiesterase 2 (Enpp2) facilitates the conversion of lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), thus enhancing the migratory activity of Mo-DCs [ 78 ]. PDZ and Lim domain protein 4 (Pdlim4) governs F-actin rearrangement and is involved in dendrite formation and is involved in CCR-JNK-mediated migration of Mo-DC [ 46 ].…”

Role of autotaxin in systemic lupus erythematosus

“…LPA has been reported to increase the production of proinflammatory cytokines, such as TNF. LPA enhances the ability of human macrophages to stimulate T cells ( 55 ), and knockdown of ATX expression in mouse macrophages impairs their migratory capacity and ability to activate T cells ( 56 ). It has also been reported that LPA modulates the differentiation of monocyte-derived DCs ( 57 ).…”