Title : Immunotherapy with oligomannose - coated liposomes ameliorates allergic 2 symptoms in a murine food allergy model

20 Background: Allergen-specific immunotherapy has been anticipated to be a 21 disease-modifying therapy for food allergies. We previously reported that CD8 + 22 regulatory T cells may prevent antigen-sensitized mice from developing allergic 23 diarrhea. Because oligomannose-coated liposomes (OML) have been shown to induce 24 MHC class I-restricted CD8 + T cell responses, we analyzed the adjuvant activities of 25 OML for inducing regulatory CD8 + T cells and mucosal tolerogenic responses in 26 allergen-sensitized mice. 27 Methods: BALB/c mice that were previously sensitized to ovalbumin (OVA) were 28 intranasally immunized with OVA-encased in OML (OVA-OML) or OVA-encased in 29 non-coated liposomes (OVA-NL). We assessed allergic diarrhea induced by oral OVA 30 administration, OVA-specific immunoglobulin production, and cytokine production in 31 the intestines and mesenteric lymph nodes (MLNs). 32 Results: Intranasal immunization with OVA-OML, but not OVA-NL, suppressed the 33 development of allergic diarrhea. This was associated with in vitro Ag-induced IL-10 34 production and the in vivo expansion of CD8 + CD28 and CD4 + CD25 + Foxp3 + T cell 35 populations among mesenteric lymph node mononuclear cells, and was significantly 36 ablated by anti-SIGNR1 or anti-CR3 mAbs. Up-regulation of serum OVA-specific IgE 37