2. Academic Validation
  3. Epithelial cells remove precancerous cells by cell competition via MHC class I-LILRB3 interaction

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

  • Nat Immunol. 2021 Nov;22(11):1391-1402. doi: 10.1038/s41590-021-01045-6.
Shiyu Ayukawa 1,  Nagisa Kamoshita  # 2,  Jun Nakayama  # 1,  Ryohei Teramoto 1,  Novalia Pishesha 3,  Kenji Ohba 4,  Nanami Sato 5,  Kei Kozawa 5,  Hikari Abe 1,  Kentaro Semba 1,  Nobuhito Goda 1,  Yasuyuki Fujita 5 6,  Takeshi Maruyama 7
Affiliations

Affiliations

  • 1 Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
  • 2 Waseda Institute for Advanced Study, Waseda University, Tokyo, Japan.
  • 3 Faculty of Arts and Sciences, Harvard University, Cambridge, MA, USA.
  • 4 Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
  • 5 Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Hokkaido, Japan.
  • 6 Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • 7 Waseda Institute for Advanced Study, Waseda University, Tokyo, Japan. [email protected].
  • # Contributed equally.
PMID: 34686865 DOI: 10.1038/s41590-021-01045-6
Abstract

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.

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