IFN-γ Secreted by CD103<SUP>+</SUP> Dendritic Cells Leads to IgG Generation in the Mesenteric Lymph Node in the Absence of Vitamin A

초록

Although the induction mechanism of secretory IgA has been well studied, that of IgG in the mucosal compartments is not well understood. In this study, vitamin A deficiency was convincingly shown to be associated with increased IgG in serum and intestinal fluid. We found increased numbers of IgG-secreting B cells in the lamina propria of the small intestine and mesenteric lymph node (MLN) of vitamin A-deficient (VAD) mice. Of note, IFN-gamma secreted by MLN dendritic cells (DCs) was significantly augmented in VAD mice, unlike control mice, and CD103(+) DCs were the main subsets to secrete IFN-gamma. The aberrant increase of IgG in VAD mice can be ascribable to IFN-gamma, because IFN-gamma(-/-) VAD mice have normal IgG levels and the addition of rIFN-gamma increased IgG production by B cells cocultured with MLN DCs from IFN-gamma(-/-) VAD mice. Oral feeding of antibiotics resulted in significant reduction of IgG in VAD mice, indicating a critical role for altered commensal bacteria for IgG class-switching recombination in the absence of vitamin A. Collectively, vitamin A deficiency provokes the generation of IFN-gamma-secreting CD103(+) DCs, which may be a critical regulator for IgG generation in the MLN. The Journal of Immunology, 2011, 186: 6999-7005.

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