Abstract
Aims:
Multiple Sclerosis (MS) is a neuroinflammatory and neurodegenerative disease affecting the central nervous system (CNS). Substantial evidence implicates a central role for CD4+ T cells in MS pathogenesis, particularly IFN-γ+ Th1 cells and IL-17+ Th17 cells. NF-κB plays an essential role in regulating the differentiation of Th1 and Th17 cells, which typically mediate inflammatory responses as self-triggers. QNZ is a highly selective inhibitor of NF-κB transcriptional activation. In this study, we assessed the impact of QNZ on CD4+ T-cell polarization in MS. Utilizing the experimental autoimmune encephalomyelitis (EAE) model, we investigated these aspects of MS.
Method:
EAE was induced in C57BL/6 female mice by active immunization with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. QNZ was injected intraperitoneally (i.p.) once every 2 days after the first immunization. Disease severity was clinically assessed and histopathologically assessed in the CNS. Phenotyping of CD4+ T cells was performed by flow cytometry in the spleen and cervical lymph nodes.
Results:
Prophylactic administration of QNZ to EAE mice suppressed the differentiation of Th1 and Th17 cells and demyelination within the spinal cord. Notably, QNZ also reduced the proportion of IFN-γ+IL-17+ Th17.1 cells, potentially playing a critical role in MS pathogenesis.
Conclusions:
Quinazoline derivative QNZ could suppress neuroinflammation, alleviate the progression of EAE and be associated with reduced Th1 and Th17 immunity.
Keywords:
QNZ; Th17 cells; Th17.1 cells; experimental autoimmune encephalomyelitis; multiple sclerosis; neuroinflammation.