Mycophenolic Acid Impedes the Antigen Presenting and Lymph Node Homing Capacities of Human Blood Myeloid Dendritic Cells

Abstract

Mycophenolic acid (MPA) is the pharmacologically active compound of the immunosuppressive drug mycophenolate mofetil. Dendritic cells (DC) are the key to initiating and priming the adaptive immune response leading to allograft rejection. We investigated the effects of MPA on human blood myeloid DC (MDC) homeostasis with a particular emphasis on their trafficking properties. Isolated peripheral blood mononuclear cells from healthy donors were cultured with MPA for 48 hr without the addition of exogenous growth factors. Flow cytometry was used for phenotypic and functional analysis of MDC within the cultured peripheral blood mononuclear cells population. Freshly isolated MDC were used for assessment of endocytotic and allostimulatory properties. Exposure to MPA decreased the expression of CC chemokine receptor (CCR)7 and increased the expression of CCR1 in MDC. In line with their CCR expression profile, MPA-treated MDC showed an enhanced migration toward inflammatory chemokines, whereas their migratory response toward lymph node chemokines decreased. MDC cultured with MPA exhibited an immature phenotype with higher endocytotic capacity, an impaired activation in response to toll-like receptor 3 ligation and loss of capacity to stimulate allogenic T cells in mixed lymphocyte reactions. MPA interferes with the initiation of acquired immunity and thus may promote allograft tolerance.