Anti-sulfated-glycan monoclonal antibody S2 inhibits lymphocyte recruitment to nasal-associated lymphoid tissues and attenuates allergic rhinitis

Abstract

Abstract Nasal-associated lymphoid tissue (NALT) is a mucosal lymphoid tissue that functions as a border of defense against inhaled antigens. Lymphocyte recruitment to NALT is mediated by the interaction between L-selectin on lymphocytes and sulfated-glycans on high endothelial venules (HEV) in NALT. HEV are specialized post capillary venules regulating lymphocyte entry form blood into parenchyma of lymphoid organs. It has been previously reported that lymphocyte recruitment to NALT was markedly blocked in HEV-expressed N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST) −1 and −2 double-deficient (DKO) mice. In the DKO mice, immune responses against nasally administered ovalbumin (OVA) including OVA-specific IgE, sneezes and nose scratches were significantly diminished. We previously generated an anti-sulfated-glycan monoclonal antibody S2 which recognizes 6-sulfo sialyl Lewis X (sLeX) and 6-sulfo sialyl N-acetyllactosamine expressed on HEV in NALT by immunizing GlcNAc6ST-1/2 DKO mice with CHO-K1 cells stably expressing 6-sulfo sLeX. S2 administration inhibited lymphocyte recruitment to NALT and allergic rhinitis induced by intranasal administration of OVA. S2 administration to OVA-immunized mice resulted in the reduction of OVA-specific serum IgE, and counts of sneezes and nose scratches after nasal immunization. Total cell numbers in NALT and expression of Th2-related cytokines such as IL-5 and IL-13 were also diminished after S2 administration. Taken together, these results suggest that S2 would serve as a novel therapeutic agent useful for the treatment of allergic rhinitis.