The role of dendritic cells in the etiology of atopic dermatitis -analysis using mouse model

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BALB/c mice were sensitized by the application of OX or TNCB solutions to the ear, then were repeatedly elicited on the original sensitized site with the same antigen. Hapten-specific ear swelling reaction was shifted from delayed hypersensitivity to early-type of the late phase reaction. Mice were divided into two groups. One group was elicited only once (acute phase), while the other group was repeatedly elicited during 24 days (chronic phase).We measured LPS-stimulated IL-1 and TNF-α production from lymphnode CD11c ^+DC obtained from acute phase or chronic phase mice, using flowcytometry. Production of both cytokines was remarkably reduced in chronic phase in comparison with acte phase. This result indicates that the number of CD11c ^+DC was reduced in chronic phase. We eliminated DC from chronic phase lymphnode cells, then added DC obtained from acute phase lymphnode cells. As a result, IFN-γ production from CD8 ^+T cells increased. Subsequently we added DC obtained from chronic phase lymphnode cells to acute phase lymphnode cells, from which DC had been eliminated. It resulted in prominent suppression of IFN-γ production from CD8 ^+T cells. These results suggest that reduction of cytokine production from DC may play an important role for inhibition of Th1 response and shift from a Th1 to a Th2 response in chronic phase lymphnode cells.Immunohistological examination revealed the number of CD11c ^+DC was reduced in chronic phase skin in comparison with acute phase one. This result is consistent with one observed in lymphnode cells.Taken together, these results indicate that in chronic phase skin and lymphnode. CD11c ^+DC fall into activation-induced cell death, leading to suppression of a Th1 response.