Regulation of inflammatory response of macrophages and induction of regulatory T cells by using retinoic acid-loaded nanostructured lipid carrier

Abstract

Immunomodulatory function of all-trans retinoic acid (ATRA) has been gathering much attention for the therapy of autoimmune diseases. ATRA is a chemically unstable molecule which requires proper formulation for targeted delivery. Here we examined nanostructured lipid carrier (NLC) for the formulation of ATRA. NLC is a representative nanoparticle formulation especially suited for oral delivery. We established the preparation procedures of ATRA-containing NLC (NLC-RA) which minimizes the degradation of ATRA during the preparation process. NLC-RA thus obtained was taken up by macrophages and induced anti-inflammatory response via suppressing NF-κB signaling as well as via enhancing the production of anti-inflammatory cytokines. Moreover, NLC-RA enhanced differentiation of naïve T cells to regulatory T cells in the co-culture system with dendritic cells. These results suggest that NLC-RA is a promising alternative therapy for the autoimmune diseases especially intestinal bowel disease.

Keywords:

• Retinoic acid
• macrophages
• regulatory T cells
• inflammatory response
• nanostructured lipid carrier

Acknowledgements

We thank Prof. Masahiro Goto for the usage of the instrument of NLC preparation. We also thank Prof. Hiroki Kakuta for his contribution in the SEAP reporter gene assay. This work was supported in part by the Kobayashi International Scholarship Foundation. K.Z. thanks MEXT scholarship for support.