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Keratan sulfate disaccharide: specific targeting to langerin and possible applications to COPD
Author(s) -
Taniguchi Naoyuki,
Ohkawa Yuki,
Fujinawa Reiko,
Kanto Noriko,
Harada Yoichiro,
Kizuka Yasuhiko
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03741
Subject(s) - langerin , keratan sulfate , c type lectin , immunology , chemistry , microbiology and biotechnology , dendritic cell , medicine , biology , immune system , glycosaminoglycan , biochemistry , chondroitin sulfate
The C‐type lectin receptor, langerin, is expressed in Langerhans cells (LCs) that are located in the dermis along with other dendritic cells (DCs). Although there have been several reports on the sugar‐binding properties of langerin, the physiological and pathological output upon the recognition of each sugar ligand by langerin are still under investigation. We propose here that the keratan sulfate (KS) disaccharide L4 and oligomeric derivatives thereof, triangle‐L4 and pendant‐L4, are functional ligands of langerin that, on binding, evoke anti‐inflammatory responses. ELISA assays revealed that triangle‐L4 and pendant‐L4 showed stronger binding to recombinant langerin than L4, and we here found that these L4 and derivatives thereof suppressed the expression of inflammatory cytokines in langerin‐expressing primary bone marrow‐derived dendritic cells (BMDCs). Furthermore, in an elastase‐induced mouse model of chronic obstructive pulmonary disease (COPD), the administration of L4 mitigated the extent of emphysema in the lung, suggesting that KS‐related langerin ligands might serve as new drug candidates for the treatment of COPD and other inflammatory diseases. We also discuss several unsolved questions that need to be tackled for our understanding of the functions of langerin and the development of langerin‐targeted therapy by using glycomimetics. Support or Funding Information This study was supported for Naoyuki Taniguchi by Japan Agency for Medical Research and Development (AMED, 18ae0101070h0003) and Grants‐in‐Aid for Scientific Research (KAKENHI KIBAN B, 15H04700 and Challenging Exploratory Research, 15K14481).