Bilirubin nanomedicine ameliorates the progression of experimental autoimmune encephalomyelitis by modulating dendritic cells

• Published in: Journal of controlled release 2021-03, Vol.331, p.74-84
• Main Authors: Kim, Tae Woo, Kim, Yujin, Jung, Wonsik, Kim, Dong Eon, Keum, Hyeongseop, Son, Youngju, Jon, Sangyong
• Format: Article
• Language: English
• Subjects: Bilirubin nanoparticles; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Reactive oxygen species; T cell differentiation; Th17 cell
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2021.01.019

Although the cause of multiple sclerosis (MS) is unclear, an autoimmune attack on myelin-based coating layers of nerve cells in the brain and spinal cord is the main feature of the disease, highlighting modulation of the immune response to myelin as a feasible therapeutic approach. Here, we report the potential of bilirubin nanoparticles (BRNPs) based on the endogenous antioxidant and anti-inflammatory agent, bilirubin, as a therapeutic nanomedicine for MS. In a mouse model of experimental autoimmune encephalomyelitis (EAE), multiple intravenous injections of BRNPs significantly delayed disease onset and suppressed disease progression and severity as well as disease incidence rate without systemic immunosuppression. Following intravenous injection, BRNPs accumulated more extensively and were retained longer in secondary lymphoid organs of EAE-induced mice compared with non-immunized control mice, including in inguinal lymph nodes (iLNs) and spleens, where antigen presenting cells (APCs) activated by the myelin antigen are abundant. Studies of the underlying mechanism of action further revealed that BRNPs negatively regulated the differentiation of naïve CD4+ T cells into T helper 17 (Th17) cells by inhibiting maturation of APCs through scavenging of reactive oxygen species (ROS) overproduced in both dendritic cells (DCs) and macrophages upon antigen uptake. These findings indicate that BRNPs have the potential to be used as a new therapeutic nanomedicine for treatment of various CD4+ T cell-associated autoimmune diseases. [Display omitted] •Experimental autoimmune encephalomyelitis is an animal model of multiple sclerosis.•Bilirubin nanoparticles possess strong antioxidant power and extended blood circulation properties.•Bilirubin nanoparticles prevent Th17 cell differentiation by inhibiting maturation of antigen presenting cells.•Intravenous injection of bilirubin nanoparticles ameliorates the progression of EAE.