| First Author | Omori S | Year | 2021 |
| Journal | Cell Rep | Volume | 34 |
| Issue | 6 | Pages | 108734 |
| PubMed ID | 33567275 | Mgi Jnum | J:317640 |
| Mgi Id | MGI:6716758 | Doi | 10.1016/j.celrep.2021.108734 |
| Citation | Omori S, et al. (2021) Tim4 recognizes carbon nanotubes and mediates phagocytosis leading to granuloma formation. Cell Rep 34(6):108734 |
| abstractText | Macrophage recognition and phagocytosis of crystals is critical for the associated fibrosis and cancer. Of note, multi-walled carbon nanotubes (MWCNTs), the highly representative products of nanotechnology, induce macrophage NLRP3 inflammasome activation and cause asbestosis-like pathogenesis. However, it remains largely unknown how macrophages efficiently recognize MWCNTs on their cell surfaces. Here, we identify by a targeted screening of phagocyte receptors the phosphatidylserine receptors T cell immunoglobulin mucin 4 (Tim4) and Tim1 as the pattern-recognition receptors for carbon crystals. Docking simulation studies reveal spatiotemporally stable interfaces between aromatic residues in the extracellular IgV domain of Tim4 and one-dimensional carbon crystals. Further, CRISPR-Cas9-mediated deletion of Tim4 and Tim1 reveals that Tim4, but not Tim1, critically contributes to the recognition of MWCNTs by peritoneal macrophages and to granuloma development in a mouse model of direct mesothelium exposure to MWCNTs. These results suggest that Tim4 recognizes MWCNTs through aromatic interactions and mediates phagocytosis leading to granulomas. |
