C-type lectin receptor MCL facilitates mincle expression and signaling through complex formation

Yasunobu Miyake, Masatsugu Oh-Hora, Sho Yamasaki

    Research output: Contribution to journalArticle

    60 Citations (Scopus)

    Abstract

    C-type lectin receptors expressed in APCs are recently defined pattern recognition receptors that play a crucial role in immune responses against pathogen-associated molecular patterns. Among pathogen-associated molecular patterns, cord factor (trehalose- 6,6'-dimycolate [TDM]) is the most potent immunostimulatory component of the mycobacterial cell wall. Two C-type lectin receptors, macrophage-inducible C-type lectin (Mincle) and macrophage C-type lectin (MCL), are required for immune responses against TDM. Previous studies indicate that MCL is required for TDM-induced Mincle expression. However, the mechanism by which MCL induces Mincle expression has not been fully understood. In this study, we demonstrate that MCL interacts with Mincle to promote its surface expression. After LPS or zymosan stimulation, MCL-deficient bone marrow-derived dendritic cells (BMDCs) had a lower level of Mincle protein expression, although mRNA expression was comparable with wild-type BMDCs. Meanwhile, BMDCs from MCL transgenic mice showed an enhanced level of Mincle expression on the cell surface. MCL was associated with Mincle through the stalk region and this region was necessary and sufficient for the enhancement of Mincle expression. This interaction appeared to be mediated by the hydrophobic repeat of MCL, as substitution of four hydrophobic residues within the stalk region with serine (MCL4S) abolished the function to enhance the surface expression of Mincle. MCL4S mutant failed to restore the defective TDM responses in MCL-deficient BMDCs. These results suggest that MCL positively regulates Mincle expression through protein-protein interaction via its stalk region, thereby magnifying Mincle-mediated signaling.

    Original languageEnglish
    Pages (from-to)5366-5374
    Number of pages9
    JournalJournal of Immunology
    Volume194
    Issue number11
    DOIs
    Publication statusPublished - Jun 1 2015

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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