title: Essential role of peripheral node addressin in lymphocyte homing to nasal-associated lymphoid tissues and allergic immune responses.
abstract: Nasal-associated lymphoid tissue (NALT) is a mucosal immune tissue that provides immune responses against inhaled antigens. Lymphocyte homing to NALT is mediated by specific interactions between lymphocytes and high endothelial venules (HEVs) in NALT. In contrast to HEVs in other mucosal lymphoid tissues, NALT HEVs strongly express peripheral node addressins (PNAds) that bear sulfated glycans recognized by the monoclonal antibody MECA-79. We investigated the role of PNAd in lymphocyte homing to NALT using sulfotransferase N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST) 1 and GlcNAc6ST-2 double knockout (DKO) mice. The expression of PNAd in NALT HEVs was eliminated in DKO mice. Short-term homing assays indicated that lymphocyte homing to NALT was diminished by 90% in DKO mice. Production of antigen-specific IgE and the number of sneezes in response to nasally administered ovalbumin were also substantially diminished. Consistently, the NALT of DKO mice showed reduced production of IL-4 and increased production of IL-10 together with an increase in CD4(+)CD25(+) regulatory T cells (T(reg) cells). Compared with the homing of CD4(+)CD25(-) conventional T cells, the homing of CD4(+)CD25(+) T(reg) cells to NALT was less dependent on the L-selectin-PNAd interaction but was partially dependent on PSGL-1 (P-selectin glycoprotein ligand 1) and CD44. These results demonstrate that PNAd is essential for lymphocyte homing to NALT and nasal allergic responses.
authors.affiliation: Laboratory of Microbiology and Immunology and Global Center of Excellence Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Ohmichi
authors.forename: Jotaro
authors.initials: J
authors.lastname: Hirakawa
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Imai
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kawashima
mesh_terms: D000818:Animals; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018928:Immunity, Mucosal; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019041:L-Selectin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016201:Receptors, Lymphocyte Homing / Q000235:genetics / Q000276:immunology; D015238:Sulfotransferases / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000097811:Carbohydrate Sulfotransferases
chemical_list: D018960:Hyaluronan Receptors; D007073:Immunoglobulin E; D016753:Interleukin-10; D015847:Interleukin-4; D019041:L-Selectin; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases; C556062:IL10 protein, mouse; C084882:P-selectin ligand protein