MGL/CD301 as a Unique C-Type Lectin Expressed on Dendritic Cells and Macrophages
Macrophage (MØ) galactose-type calcium-type lectin, MGL, also termed CD301 or Clec10A, is a type 2 transmembrane glycoprotein having a calcium-dependent carbohydrate recognition domain. Orthologous genes seem to be present throughout the vertebrates, and the lectin binds galactose and N-acetylgalactosamine among monosaccharides. Although mammalian MGL resembles the hepatic asialoglycoprotein receptor in its structure and its carbohydrate specificity, the cellular distribution of MGL is limited to specific subsets of dendritic cells (DCs) and MØs. Mouse MGL2, apparently the direct counterpart of human MGL, strongly binds clusters of carbohydrate chains with terminal N-acetylgalactosamine residues, a molecular feature characteristic to mucins. MGL was also shown to recognize carbohydrate chains from exogenous organisms. Comparisons of various oligosaccharides for their binding and identification of ligands/counter receptors by biochemical means strongly suggest that the important structural features recognized by MGL depend on the biological context. It is also likely that MGL functions on DCs to recognize and distinguish the self, altered self, pathogens, and commensal organisms, and that the regulatory outcomes depend on the unique nature of the DC/MØ subsets. Mice lacking the Mgl1 or Mgl2 gene do not show any abnormality as long as they are maintained under a controlled environment. However, upon encountering a pathogenic insult, they show a variety of outcomes depending on the organ sites and the type of the insult. Further investigations are necessary to explore how endogenous ligand/counter receptors are involved in the regulation of immunological and inflammatory responses by MGL.
KeywordsMGL (CD301) Calcium-type lectin Dendritic cells Macrophages Tissue inflammation Carbohydrate ligands
The authors would like to acknowledge those who are engaged with the studies introduced in this chapter and collaborators, particularly Dr. Steve Hedrick for Mgl1–/– mice and Dr. Paul Crocker, for contributing unpublished data. We would also like to acknowledge Dr. Katrin Ishii-Schrade and Ms. Miki Noji in the preparation of this manuscript. The work is supported by JSPS KAKENHI Grants to KDN and TI.
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