Epithelial cells remove precancerous cells by cell competition via MHC class I–LILRB3 interaction

Shiyu Ayukawa, Nagisa Kamoshita, Jun Nakayama, Ryohei Teramoto, Novalia Pishesha, Kenji Ohba, Nanami Sato, Kei Kozawa, Hikari Abe, Kentaro Semba, Nobuhito Goda, Yasuyuki Fujita, Takeshi Maruyama*

*この研究の対応する著者

研究成果: Article査読

8 被引用数 (Scopus)

抄録

Epithelial cells have an ability termed ‘cell competition’, which is an immune surveillance-like function that extrudes precancerous cells from the epithelial layer, leading to apoptosis and clearance. However, it remains unclear how epithelial cells recognize and extrude transformed cells. Here, we discovered that a PirB family protein, leukocyte immunoglobulin-like receptor B3 (LILRB3), which is expressed on non-transformed epithelial cells, recognizes major histocompatibility complex class I (MHC class I) that is highly expressed on transformed cells. MHC class I interaction with LILRB3 expressed on normal epithelial cells triggers an SHP2–ROCK2 pathway that generates a mechanical force to extrude transformed cells. Removal of transformed cells occurs independently of natural killer (NK) cell or CD8+ cytotoxic T cell-mediated activity. This is a new mechanism in that the immunological ligand–receptor system generates a mechanical force in non-immune epithelial cells to extrude precancerous cells in the same epithelial layer.

本文言語English
ページ(範囲)1391-1402
ページ数12
ジャーナルNature Immunology
22
11
DOI
出版ステータスPublished - 2021 11月

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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