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Analysis of hypoxia-associated dendritic cells in colitic mice and effects of probiotics on IL-10 production in inflammatory dendritic-cells under hypoxia

In: Beneficial Microbes
Authors:
T. Ogita Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-hiroshima, Hiroshima 739- 8528, Japan.
Department of Interdisciplinary Genome Sciences and Cell Metabolism, Institute for Biomedical Sciences, Inderdisciplinary Cluster for Cutting Edge Research, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Japan.

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J. Miyamoto Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-hiroshima, Hiroshima 739- 8528, Japan.
Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo 183-0057, Japan.

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Y. Hirabayashi Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-hiroshima, Hiroshima 739- 8528, Japan.

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M. Rossi Istituto di Scienze dell’Alimentazione, CNR, via Roma 64, 83100 Avellino, Italy.

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G. Mazzarella Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-hiroshima, Hiroshima 739- 8528, Japan.

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I. Takahashi Department of Mucosal Immunology, Faculty of Dentistry, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.

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S. Tanabe Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-hiroshima, Hiroshima 739- 8528, Japan.

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T. Suzuki Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-hiroshima, Hiroshima 739- 8528, Japan.

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The aim of this study was to analyse hypoxia-associated dendritic cells (DCs) in colitic mice and the effects of probiotics on interleukin (IL)-10 production in inflammatory DCs under hypoxic conditions. Extensive hypoxia was observed in the colonic mucosa of dextran sodium sulphate-induced colitic mice. Flow cytometric analysis demonstrated that hypoxia-inducible factor-1α+ DCs in colonic lamina propria (CLP) lymphocytes and mesenteric lymph nodes (MLN) were more abundant in colitic mice than those in controls. Among three subsets of DCs, i.e. plasmacytoid DCs, conventional DCs (cDCs), and monocyte-derived DCs (mDCs), cDCs and mDCs were more abundant in CLP of colitic mice. Bone marrow-derived Flt-3L-induced DCs (Flt-DCs) but not bone marrow-derived GM-CSF-induced DCs (GM-DCs), incubated with 1% O2 exhibited an inflammatory phenotype, with higher CD86, IL-6, and tumour necrosis factor-α expression, and lower IL-10 levels than those in Flt-DCs incubated with 21% O2. The hypoxia-induced decrease in IL-10 expression in Flt-DCs was restored by Bifidobacterium bifidum JCM 1255T promoted IL-10 expression through the p38 pathway under normoxic conditions. The anti-inflammatory effects of B. bifidum JCM 1255T in Flt-DCs were mediated through different cellular mechanisms under hypoxic and normoxic conditions. B. bifidum JCM 1255T could be used therapeutically for its anti-inflammatory effects.

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