Carbon nanospheres mediated delivery of nuclear matrix protein SMAR1 to direct experimental autoimmune encephalomyelitis in mice

Abstract

Owing to the suppression of immune responses and associated side effects, steroid based treatments for inflammatory encephalitis disease can be detrimental. Here, we demonstrate a novel carbon nanosphere (CNP) based treatment regime for encephalomyelitis in mice by exploiting the functional property of the nuclear matrix binding protein SMAR1. A truncated part of SMAR1 ie, the DNA binding domain was conjugated with hydrothermally synthesized CNPs. When administered intravenously, the conjugate suppressed experimental animal encephalomyelitis in T cell specific conditional SMAR1 knockout mice (SMAR −/− ). Further, CNP-SMAR1 conjugate delayed the onset of the disease and reduced the demyelination significantly. There was a significant decrease in the production of IL-17 after re-stimulation with MOG. Altogether, our findings suggest a potential carbon nanomaterial based therapeutic intervention to combat Th17 mediated autoimmune diseases including experimental autoimmune encephalomyelitis.

Chromatin Remodeling Protein SMAR1 Is a Critical Regulator of T Helper Cell Differentiation and Inflammatory Diseases

“…Our lab has also reported that SMAR1 regulates STAT3 gene expression by directly binding to STAT3 promoter and recruiting the repressor complex ( 89 ). In agreement with this, a deficiency of SMAR1 in T cells renders the mice susceptible to myelin oligodendrocyte glycoprotein peptide-driven EAE disease with higher pro-inflammatory IL-17-producing T cells ( 105 ). EAE is an animal model of human CNS demyelinating disease, including multiple sclerosis (MS).…”

“…EAE disease progression can be controlled by signaling molecules or transcription factor that prevents Th17 generation ( 106 , 107 ). We have shown using a nanoparticle-mediated delivery that SMAR1 controls the Th17 generation and EAE disease progression ( 105 ). The small size and high surface volumes of nanoparticles makes them a convenient route of drugs/proteins delivery inside the cell ( 108 ).…”

“…We observed CNP-mediated delivery of SMAR1 represses the EAE disease progression by inhibiting the IL-17 expression from T cells (Figure 4 ). Recent study from our lab has shown that nanoparticle-mediated SMAR1 delivery could potentially be used to suppress auto-inflammatory diseases ( 105 ). As a treatment for MS, CNP-SMAR1 has three therapeutic values (i) opposition of Th17 differentiation, (ii) increment in the anti-inflammatory IL-10 production by favoring T reg differentiation, and (iii) promotion of the self-tolerance to myelin.…”

Nuclear Matrix-associated Protein SMAR1 Attenuated Acute Graft-versus-host Disease by Targeting JAK-STAT Signaling in CD4+ T Cells

“…10 SMAR-1-binding protein (SMAR1; also know as BANP) is considered an immunomodulator and has been studied for its role in the immune response in a variety of immune diseases. [11][12][13] The specialized effector subsets of T cells that differentiate from naive T cells into mature cells are closely related to SMAR1. 14 Our clinical samples showed that SMAR1 was significantly downregulated in the CD4 + T cells of aGVHD patients and related to the occurrence of aGVHD.…”

“…10 SMAR-1–binding protein (SMAR1; also know as BANP) is considered an immunomodulator and has been studied for its role in the immune response in a variety of immune diseases. 11-13 The specialized effector subsets of T cells that differentiate from naive T cells into mature cells are closely related to SMAR1. 14…”