MGL/CD301 as a Unique C-Type Lectin Expressed on Dendritic Cells and Macrophages

  • Kaori Denda-Nagai
  • Tatsuro IrimuraEmail author


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.


MGL (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 Paul Crocker, for contributing unpublished data.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.


  1. Chun KH, Imai Y, Higashi N, Irimura T (2000) Migration of dermal cells expressing a macrophage C-type lectin during the sensitization phase of delayed-type hypersensitivity. J Leukoc Biol 68:471–478PubMedGoogle Scholar
  2. Denda-Nagai K, Aida S, Saba K, Suzuki K, Moriyama S, Oo-Puthinan S, Tsuiji M, Morikawa A, Kumamoto Y, Sugiura D, Kudo A, Akimoto Y, Kawakami H, Bovin NV, Irimura T (2010) Distribution and function of macrophage galactose-type C-type lectin 2 (MGL2/CD301b): efficient uptake and presentation of glycosylated antigens by dendritic cells. J Biol Chem 285:19193–19204CrossRefPubMedPubMedCentralGoogle Scholar
  3. Denda-Nagai K, Kubota N, Tsuiji M, Kamata M, Irimura T (2002) Macrophage C-type lectin on bone marrow-derived immature dendritic cells is involved in the internalization of glycosylated antigens. Glycobiology 12(7):443–450CrossRefPubMedGoogle Scholar
  4. Drickamer K (1993) Recognition of complex carbohydrates by Ca(2+)-dependent animal lectins. Biochem Soc Trans 21(2):456–459CrossRefPubMedGoogle Scholar
  5. Gao Y, Nish SA, Jiang R, Hou L, Licona-Limón P, Weinstein JS, Zhao H, Medzhitov R (2013) Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells. Immunity 39(4):722–732CrossRefPubMedPubMedCentralGoogle Scholar
  6. Higashi N, Fujioka K, Denda-Nagai K, Hashimoto S, Nagai S, Sato T, Fujita Y, Morikawa A, Tsuiji M, Miyata-Takeuchi M, Sano Y, Suzuki N, Yamamoto K, Matsushima K, Irimura T (2002) The macrophage C-type lectin specific for galactose/N-acetylgalactosamine is an endocytic receptor expressed on monocyte-derived immature dendritic cells. J Biol Chem 277(23):20686–20693CrossRefPubMedGoogle Scholar
  7. Ii M, Kawasaki T, Yamashina I (1988) Structural similarity between the macrophage lectin specific for galactose/N-acetylgalactosamine and the hepatic asialoglycoprotein binding protein. Biochem Biophys Res Commun 155(2):720–725CrossRefPubMedGoogle Scholar
  8. Ii M, Kurata H, Itoh N, Yamashina I, Kawasaki T (1990) Molecular cloning and sequence analysis of cDNA encoding the macrophage lectin specific for galactose and N-acetylgalactosamine. J Biol Chem 265(19):11295–11298PubMedGoogle Scholar
  9. Iida S, Yamamoto K, Irimura T (1999) Interaction of human macrophage C-type lectin with O-linked N-acetylgalactosamine residues on mucin glycopeptides. J Biol Chem 274(16):10697–10705CrossRefPubMedGoogle Scholar
  10. Imamura T, Toyoshima S, Osawa T (1984) Lectin-like molecules on the murine macrophage cell surface. Biochim Biophys Acta 805:235–244CrossRefPubMedGoogle Scholar
  11. Kimura T, Imai Y, Irimura T (1995) Calcium-dependent conformation of a mouse macrophage calcium-type lectin. Carbohydrate binding activity is stabilized by an antibody specific for a calcium-dependent epitope. J Biol Chem 270:16056–16062CrossRefPubMedGoogle Scholar
  12. Kumamoto Y, Higashi N, Denda-Nagai K, Tsuiji M, Sato K, Crocker PR, Irimura T (2004) Identification of sialoadhesin as a dominant lymph node counter-receptor for mouse macrophage galactose-type C-type lectin 1. J Biol Chem 279:49274–49280CrossRefPubMedGoogle Scholar
  13. Kumamoto Y, Denda-Nagai K, Aida S, Higashi N, Irimura T (2009) MGL2 dermal dendritic cells are sufficient to initiate contact hypersensitivity in vivo. PLoS One 4:e5619CrossRefPubMedPubMedCentralGoogle Scholar
  14. Kumamoto Y, Linehan M, Weinstein JS, Laidlaw BJ, Craft JE, Iwasaki A (2013) CD301b(+) dermal dendritic cells drive T helper 2 cell-mediated immunity. Immunity 39(4):733–743CrossRefPubMedGoogle Scholar
  15. Mizuochi S, Akimoto Y, Imai Y, Hirano H, Irimura T (1997) Unique tissue distribution of a mouse macrophage C-type lectin. Glycobiology 7(1):137–146CrossRefPubMedGoogle Scholar
  16. Mizuochi S, Akimoto Y, Imai Y, Hirano H, Irimura T (1998) Immunohistochemical study on a macrophage calcium-type lectin in mouse embryos: transient expression in chondroblasts during endochondral ossification. Glycoconj J 15(4):397–404CrossRefPubMedGoogle Scholar
  17. Murakami R, Denda-Nagai K, Hashimoto S, Nagai S, Hattori M, Irimura T (2013) A unique dermal dendritic cell subset that skews the immune response toward Th2. PLoS One 8(9):e73270CrossRefPubMedPubMedCentralGoogle Scholar
  18. Oda S, Sato M, Toyoshima S, Osawa T (1988) Purification and characterization of a lectin-like molecule specific for galactose/N-acetyl-galactosamine from tumoricidal macrophages. J Biochem 104(4):600–605PubMedGoogle Scholar
  19. Onami TM, Lin MY, Page DM, Reynolds SA, Katayama CD, Marth JD, Irimura T, Varki A, Varki N, Hedrick SM (2002) Generation of mice deficient for macrophage galactose- and N-acetylgalactosamine-specific lectin: limited role in lymphoid and erythroid homeostasis and evidence for multiple lectins. Mol Cell Biol 22:5173–5181CrossRefPubMedPubMedCentralGoogle Scholar
  20. Oo-Puthinan S, Maenuma K, Sakakura M, Denda-Nagai K, Tsuiji M, Shimada I, Nakamura-Tsuruta S, Hirabayashi J, Bovin NV, Irimura T (2008) The amino acids involved in the distinct carbohydrate specificities between macrophage galactose-type C-type lectins 1 and 2 (CD301a and b) of mice. Biochim Biophys Acta 1780:89–100CrossRefPubMedGoogle Scholar
  21. Saba K, Denda-Nagai K, Irimura T (2009) A C-type lectin MGL1/CD301a plays an anti-inflammatory role in murine experimental colitis. Am J Pathol 174:144–152CrossRefPubMedPubMedCentralGoogle Scholar
  22. Sakakura M, Oo-Puthinan S, Moriyama C, Kimura T, Moriya J, Irimura T, Shimada I (2008) Carbohydrate binding mechanism of the macrophage galactose-type C-type lectin 1 revealed by saturation transfer experiments. J Biol Chem 283:33665–33673CrossRefPubMedPubMedCentralGoogle Scholar
  23. Sano Y, Usami K, Izawa R, Denda-Nagai K, Higashi N, Kimura T, Suzuki N, Irimura T (2007) Properties of blocking and non-blocking monoclonal antibodies specific for human macrophage galactose-type C-type lectin (MGL/ClecSF10A/CD301). J Biochem 141:127–136CrossRefPubMedGoogle Scholar
  24. Sato M, Kawakami K, Osawa T, Toyoshima S (1992) Molecular cloning and expression of cDNA encoding a galactose/N-acetylgalactosamine-specific lectin on mouse tumoricidal macrophages. J Biochem 111:331–336PubMedGoogle Scholar
  25. Sato K, Imai Y, Higashi N, Kumamoto Y, Onami TM, Hedrick SM, Irimura T (2005) Lack of antigen-specific tissue remodeling in mice deficient in the macrophage galactose-type calcium-type lectin 1/CD301a. Blood 106:207–215CrossRefPubMedGoogle Scholar
  26. Suzuki N, Yamamoto K, Toyoshima S, Osawa T, Irimura T (1996) Molecular cloning and expression of cDNA encoding human macrophage C-type lectin. Its unique carbohydrate binding specificity for Tn antigen. J Immunol 156:128–135PubMedGoogle Scholar
  27. Takada A, Fujioka K, Tsuiji M, Morikawa A, Higashi N, Ebihara H, Kobasa D, Feldmann H, Irimura T, Kawaoka Y (2004) Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry. J Virol 78(6):2943–2947CrossRefPubMedPubMedCentralGoogle Scholar
  28. Tsuiji M, Fujimori M, Ohashi Y, Higashi N, Onami TM, Hedrick SM, Irimura T (2002) Molecular cloning and characterization of a novel mouse macrophage C-type lectin, mMGL2, which has a distinct carbohydrate specificity from mMGL1. J Biol Chem 277:28892–28901CrossRefPubMedGoogle Scholar
  29. Upham JP, Pickett D, Irimura T, Anders EM, Reading PC (2010) Macrophage receptors for influenza A virus: role of the macrophage galactose-type lectin and mannose receptor in viral entry. J Virol 84:3730–3737CrossRefPubMedPubMedCentralGoogle Scholar
  30. Yamamoto K, Ishida C, Shinohara Y, Hasegawa Y, Konami Y, Osawa T, Irimura T (1994) Interaction of immobilized recombinant mouse C-type macrophage lectin with glycopeptides and oligosaccharides. Biochemistry 33(26):8159–8166CrossRefPubMedGoogle Scholar
  31. Yuita H, Tsuiji M, Tajika Y, Matsumoto Y, Hirano K, Suzuki N, Irimura T (2005) Retardation of removal of radiation-induced apoptotic cells in developing neural tubes in macrophage galactose-type C-type lectin-1-deficient mouse embryos. Glycobiology 15(12):1368–1375CrossRefPubMedGoogle Scholar
  32. Zola H, Swart B, Nicholson I, Aasted B, Bensussan A, Boumsell L, Buckley C, Clark G, Drbal K, Engel P, Hart D, Horejsi V, Isacke C, Macardle P, Malavasi F, Mason D, Olive D, Saalmueller A, Schlossman SF, Schwartz-Albiez R, Simmons P, Tedder TF, Uguccioni M, Warren H (2005) CD molecules 2005: human cell differentiation molecules. Blood 106:3123–3126CrossRefPubMedGoogle Scholar

Copyright information

© Springer Japan 2016

Authors and Affiliations

  1. 1.Juntendo University School of MedicineTokyoJapan

Personalised recommendations