Dataset Information

A novel monoclonal antibody against 6-sulfo sialyl Lewis x glycans attenuates murine allergic rhinitis by suppressing Th2 immune responses.

ABSTRACT: Lymphocyte homing is mediated by the interaction between L-selectin on lymphocytes and its glycoprotein ligands modified with 6-sulfo sialyl Lewis x (6-sulfo sLe^x) glycans on high endothelial venules (HEVs) in peripheral lymph nodes (PLNs). However, the lack of specific antibodies reactive with both human and mouse 6-sulfo sLe^x has limited our understanding of its function in vivo. Here, we generated a novel monoclonal antibody, termed SF1, that specifically reacts with 6-sulfo sLe^x expressed on HEVs in both species in a manner dependent on sulfate, fucose, and sialic acid modifications. Glycan array and biolayer interferometry analyses indicated that SF1 specifically bound to 6-sulfo sLe^x with a dissociation constant of 6.09 × 10^-9 M. SF1 specifically bound to four glycoproteins from PLNs corresponding to the molecular sizes of L-selectin ligand glycoproteins. Consistently, SF1 inhibited L-selectin-dependent lymphocyte rolling on 6-sulfo sLe^x-expressing cells ex vivo and lymphocyte homing to PLNs and nasal-associated lymphoid tissues in vivo. Furthermore, SF1 significantly attenuated ovalbumin-induced allergic rhinitis in mice in association with significant suppression of Th2 immune responses. Collectively, these results suggest that SF1 can be useful for the functional analysis of 6-sulfo sLe^x and may potentially serve as a novel therapeutic agent against immune-related diseases.

SUBMITTER: Liu W

PROVIDER: S-EPMC10514285 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A novel monoclonal antibody against 6-sulfo sialyl Lewis x glycans attenuates murine allergic rhinitis by suppressing Th2 immune responses.

Liu Wei W Xiong Wei W Liu Wenxin W Hirakawa Jotaro J Kawashima Hiroto H

Scientific reports 20230921 1

Lymphocyte homing is mediated by the interaction between L-selectin on lymphocytes and its glycoprotein ligands modified with 6-sulfo sialyl Lewis x (6-sulfo sLe<sup>x</sup>) glycans on high endothelial venules (HEVs) in peripheral lymph nodes (PLNs). However, the lack of specific antibodies reactive with both human and mouse 6-sulfo sLe<sup>x</sup> has limited our understanding of its function in vivo. Here, we generated a novel monoclonal antibody, termed SF1, that specifically reacts with 6-s ...[more]

PMID: 37735247

Similar Datasets

Project description:Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. These carbohydrates differ from those of the surrounding non-cancerous tissues and contribute to the malignant phenotype of the cancer cells by promoting proliferation, metastasis, and immunosuppression. However, due to tumor tissue heterogeneity and technological limitations, TACAs are insufficiently explored. Methods: A workflow was established to decode the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts. Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. The released O-glycans were analyzed by porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode. Results: Distinctive O-glycosylation features were found in cancerous, stromal and normal colon mucosal regions. Over 100 O-linked glycans were detected in cancerous regions with absence in normal mucosa. From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. In contrast, normal colon mucosa predominantly expressed core 3 O-glycans, carrying α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens. Conclusion: In this study, we present a novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa. These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC.

Dataset Information

A novel monoclonal antibody against 6-sulfo sialyl Lewis x glycans attenuates murine allergic rhinitis by suppressing Th2 immune responses.

Publications

A novel monoclonal antibody against 6-sulfo sialyl Lewis x glycans attenuates murine allergic rhinitis by suppressing Th2 immune responses.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets