Details

Autor(en) / Beteiligte

• Omori, Satoshi
• Tsugita, Misato
• Hoshikawa, Yasuto
• Morita, Masanobu
• Ito, Fumiya
• Yamaguchi, Shin-Ichiro
• Xie, Qilin
• Noyori, Osamu
• Yamaguchi, Tomoya
• Takada, Ayato
• Saitoh, Tatsuya
• Toyokuni, Shinya
• Akiba, Hisaya
• Nagata, Shigekazu
• Kinoshita, Kengo
• Nakayama, Masafumi

Titel

Tim4 recognizes carbon nanotubes and mediates phagocytosis leading to granuloma formation

Ist Teil von

• Cell reports (Cambridge), 2021-02, Vol.34 (6), p.108734, Article 108734

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Tim4 and Tim1 recognize carbon nanomaterials including MWCNTs•Aromatic-aromatic interactions stabilize the direct binding of Tim4 to MWCNTs•Tim4 is involved in MWCNT recognition by macrophages•Tim4-mediated phagocytosis of MWCNTs leads to granuloma formation Needle-like multi-walled carbon nanotubes (MWCNTs) are engulfed by macrophages, which cause inflammation and asbestosis-like pathogenesis in rodents; however, how macrophages recognize MWCNTs remains unclear. Omori et al. demonstrate that Tim4 recognizes MWCNTs through aromatic-aromatic interactions and mediates macrophage phagocytosis leading to granulomas.