Immunosuppressive biomaterial-based therapeutic vaccine to treat multiple sclerosis via re-establishing immune tolerance.
Thanh Loc NguyenYoungjin ChoiJihye ImHyunsu ShinNgoc Man PhanMin Kyung KimSeung Woo ChoiJaeyoon KimPublished in: Nature communications (2022)
Current therapies for autoimmune diseases, such as multiple sclerosis (MS), induce broad suppression of the immune system, potentially promoting opportunistic infections. Here, we report an immunosuppressive biomaterial-based therapeutic vaccine carrying self-antigen and tolerance-inducing inorganic nanoparticles to treat experimental autoimmune encephalomyelitis (EAE), a mouse model mimicking human MS. Immunization with self-antigen-loaded mesoporous nanoparticles generates Foxp3 + regulatory T-cells in spleen and systemic immune tolerance in EAE mice, reducing central nervous system-infiltrating antigen-presenting cells (APCs) and autoreactive CD4 + T-cells. Introducing reactive oxygen species (ROS)-scavenging cerium oxide nanoparticles (CeNP) to self-antigen-loaded nanovaccine additionally suppresses activation of APCs and enhances antigen-specific immune tolerance, inducing recovery in mice from complete paralysis at the late, chronic stage of EAE, which shows similarity to chronic human MS. This study clearly shows that the ROS-scavenging capability of catalytic inorganic nanoparticles could be utilized to enhance tolerogenic features in APCs, leading to antigen-specific immune tolerance, which could be exploited in treating MS.
Keyphrases
- multiple sclerosis
- regulatory t cells
- reactive oxygen species
- mass spectrometry
- dendritic cells
- oxide nanoparticles
- endothelial cells
- ms ms
- mouse model
- white matter
- drug delivery
- cell death
- dna damage
- induced apoptosis
- induced pluripotent stem cells
- immune response
- signaling pathway
- type diabetes
- cancer therapy
- high fat diet induced
- metabolic syndrome
- insulin resistance
- walled carbon nanotubes
- tissue engineering
- oxidative stress
- metal organic framework
- cell proliferation