All-trans-Retinoic Acid Imprints Expression of the Gut-Homing Marker alpha 4 beta 7 while Suppressing Lymph Node Homing of Dendritic Cells

• Published in: Clinical and vaccine immunology 2013-10, Vol.20 (10), p.1642-1646
• Main Authors: Evans, Tristan I, Reeves, R Keith
• Format: Article
• Language: English
• Subjects: Adjuvants; Macaca mulatta
• ISSN: 1556-679X
• DOI: 10.1128/CVI.00419-13

Tissue-directed trafficking of dendritic cells (DCs) as natural adjuvants and/or direct vaccine carriers is highly attractive for the next generation of vaccines and immunotherapeutics. Since these types of studies would undoubtedly be first conducted using nonhuman primate models, we evaluated the ability of all-trans-retinoic acid (ATRA) to induce gut-homing alpha 4 beta 7 expression on rhesus macaque plasmacytoid and myeloid DCs (pDCs and mDCs, respectively). Induction of alpha 4 beta 7 occurred in both a time-dependent and a dose-dependent manner with up to 8-fold increases for mDCs and 2-fold increases for pDCs compared to medium controls. ATRA treatment was also specific in inducing alpha 4 beta 7 expression, but not expression of another mucosal trafficking receptor, CCR9. Unexpectedly, upregulation of alpha 4 beta 7 was associated with a concomitant downregulation of CD62L, a marker of lymph node homing, indicating an overall shift in the trafficking repertoire. These same phenomena occurred with ATRA treatment of human and chimpanzee DCs, suggesting a conserved mechanism among primates. Collectively, these data serve as a first evaluation for ex vivo modification of primate DC homing patterns that could later be used in reinfusion studies for the purposes of immunotherapeutics or mucosa-directed vaccines.