| First Author | Li F | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 6718 |
| PubMed ID | 37872182 | Mgi Jnum | J:343050 |
| Mgi Id | MGI:7544536 | Doi | 10.1038/s41467-023-42216-3 |
| Citation | Li F, et al. (2023) C-type lectin receptor 2d forms homodimers and heterodimers with TLR2 to negatively regulate IRF5-mediated antifungal immunity. Nat Commun 14(1):6718 |
| abstractText | Dimerization of C-type lectin receptors (CLRs) or Toll-like receptors (TLRs) can alter their ligand binding ability, thereby modulating immune responses. However, the possibilities and roles of dimerization between CLRs and TLRs remain unclear. Here we show that C-type lectin receptor-2d (CLEC2D) forms homodimers, as well as heterodimers with TLR2. Quantitative ligand binding assays reveal that both CLEC2D homodimers and CLEC2D/TLR2 heterodimers have a higher binding ability to fungi-derived beta-glucans than TLR2 homodimers. Moreover, homo- or hetero-dimeric CLEC2D mediates beta-glucan-induced ubiquitination and degradation of MyD88 to inhibit the activation of transcription factor IRF5 and subsequent IL-12 production. Clec2d-deficient female mice are resistant to infection with Candida albicans, a human fungal pathogen, owing to the increase of IL-12 production and subsequent generation of IFN-gamma-producing NK cells. Together, these data indicate that CLEC2D forms homodimers or heterodimers with TLR2, which negatively regulate antifungal immunity through suppression of IRF5-mediated IL-12 production. These homo- and hetero-dimers of CLEC2D and TLR2 provide an example of receptor dimerization to regulate host innate immunity against microbial infections. |
