Clec10a regulates mite-induced dermatitis

Sci Immunol. 2019 Dec 6;4(42):eaax6908. doi: 10.1126/sciimmunol.aax6908.


House dust mite (HDM) is a major allergen that causes allergic diseases such as atopic dermatitis. However, the regulatory mechanisms of HDM-induced immune responses are incompletely understood. NC/Nga mice are an inbred strain that is more susceptible to HDM and develops more severe dermatitis than other strains. Using whole-exome sequencing, we found that NC/Nga mice carry a stop-gain mutation in Clec10a, which encodes a C-type lectin receptor, Clec10a (MGL1/CD301a). The repair of this gene mutation using the CRISPR-Cas9 system ameliorated HDM-induced dermatitis, indicating that the Clec10a mutation is responsible for hypersensitivity to HDM in NC/Nga mice. Similarly, Clec10a -/- mice on the C57BL/6J background showed exacerbated HDM-induced dermatitis. Clec10a expressed on skin macrophages inhibits HDM-induced Toll-like receptor 4 (TLR4)-mediated inflammatory cytokine production through the inhibitory immunoreceptor tyrosine activating motif in its cytoplasmic portion. We identified asialoglycoprotein receptor 1 (Asgr1) as a functional homolog of mouse Clec10a in humans. Moreover, we found that a mucin-like molecule in HDM is a ligand for mouse Clec10a and human Asgr1. Skin application of the ligand ameliorated a TLR4 ligand-induced dermatitis in mice. Our findings suggest that Clec10a in mice and Asgr1 in humans play an important role in skin homeostasis against inflammation associated with HDM-induced dermatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology*
  • Animals
  • Asialoglycoprotein Receptor / genetics
  • Asialoglycoprotein Receptor / immunology*
  • Asialoglycoproteins / genetics
  • Asialoglycoproteins / immunology*
  • Dermatitis, Atopic / immunology*
  • Female
  • Humans
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology*
  • Leukocytes, Mononuclear / immunology
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation
  • Pyroglyphidae / immunology*
  • Toll-Like Receptor 4 / immunology


  • ASGR1 protein, human
  • Allergens
  • Asialoglycoprotein Receptor
  • Asialoglycoproteins
  • Clec10a protein, mouse
  • Lectins, C-Type
  • Membrane Proteins
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4