Alteration of Innate Immune T and B Cells in the NC/Nga Mouse

ABSTRACT

BACKGROUND: Millions of people in the world are suffering from atopic dermatitis (AD), which is a chronic inflammatory skin disease triggered by Th2 immune responses. The NC/Nga mouse is the most extensively studied animal model of AD. Like human AD, NC/Nga mice demonstrate increased levels of IgE, a hallmark of Th2 immune responses. Adaptive immunity cannot be generated without help of innate immunity. Especially natural killer T (NKT) cells and marginal zone B (MZB) cells have been known to play important roles in linking innate immunity to adaptive immunity. METHODS: Through flow cytometric analysis and ELISA assay, we investigated whether these lymphocytes might be altered in number in NC/Nga mice. RESULTS: Our data demonstrated that the number of NKT cells was reduced in NC/Nga mice and IFNgamma production by NKT cells upon alpha-GalCer stimulation decreased to the levels of CD1d KO mice lacking in NKT cells. However, reduction of NKT cells in NC/Nga mice was not due to CD1d expression, which was normal in the thymus. Interestingly, there was a significant increase of CD1d(high)B220+ cells in the spleen of NC/Nga mice. Further, we confirmed that CD1d(high)B220+ cells are B cells, not dendritic cells. These CD1d(high)B220+ B cells show IgM(high)CD21(high)CD23low, a characteristic phenotype of MZB cells. CONCLUSION: We provide the evidence that there are decreased activities of NKT cells and increased number of MZB cells in the NC/Nga mice. Our findings may thus explain why NC/Nga mice are susceptible to AD.