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Sublingual administration of Lactobacillus paracasei KW3110 inhibits Th2-dependent allergic responses via upregulation of PD-L2 on dendritic cells
Authors:Inamine Ayako  Sakurai Daijyu  Horiguchi Shigetoshi  Yonekura Syuji  Hanazawa Toyoyuki  Hosokawa Hiroyuki  Matuura-Suzuki Asaka  Nakayama Toshinori  Okamoto Yoshitaka
Institution:Department of Otolaryngology, Head and Neck Surgery (J2), Graduate School of Medicine, Chiba University, Chiba, Japan. ainamine@faculty.chiba-u.jp
Abstract:Lactic acid bacteria have potential in immunomodulation therapy, but their clinical efficacy and underlying mechanisms are unclear. We aimed to clarify the anti-allergic immune responses induced by intragastric and sublingual administration of heat-killed Lactobacillus paracasei KW3110 and Lactobacillus acidophilus L-92. The KW3110 strain (but not the L-92 strain) enhanced ovalbumin (OVA)-induced expression of CCR-7 and PD-L2 in murine dendritic cells (DCs), and strongly inhibited IL-5 and IL-13 production in vitro in co-cultures with Th2-skewed CD4(+) T cells from DO11.10 transgenic mice. Sublingual administration of low-dose KW3110 (but not L-92) to OVA-sensitized mice selectively suppressed serum IgE production and Th2 cytokine expression in cervical lymph nodes, and significantly improved symptoms after OVA provocation in vivo. KW3110 probably accelerates DC migration into the regional lymph nodes and inhibits Th2 cytokine production through enhanced CCR-7 and PD-L2 expression. Thus, sublingual KW3110 administration may be effective in reducing allergic inflammation.
Keywords:PBMC  Peripheral blood mononuclear cell  SLIT  Sublingual immunotherapy  DC  Dendritic cell  OVA  Ovalbumin  BM  Bone marrow  LPS  Lipopolysaccharide  CLN  Cervical lymph node  ILN  Inguinal lymph node  ELISA  Enzyme-linked immunosorbent assay  ELISPOT  Enzyme-linked immunospot  TLR  Toll-like receptor  LGG  Lactobacillus rhamnosus GG  FACS  Fluorescein-activated cell sorter  FITC  Fluorescein isothiocyanate  GM-CSF  Granulocyte macrophage colony-stimulating factor  TCR  T cell receptor  OD  Optical density
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