IRCCS Humanitas Research Hospital & Humanitas University
Published March 12, 2025 | Version v1
Dataset Open

Dataset related to article "Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells"

Creators

  • 1. ROR icon IRCCS Humanitas Research Hospital
  • 2. ROR icon Karolinska Institutet
  • 3. EDMO icon National Research Council
  • 4. ROR icon Humanitas University
  • 5. ROR icon IRCCS Ospedale San Raffaele
  • 6. ROR icon University of Milan
  • 7. ROR icon University of Palermo
  • 8. ROR icon Sapienza University of Rome
  • 9. ROR icon William Harvey Research Institute

Description

Neutrophils are the most abundant leukocytes in human blood and play a primary role in resistance against invading microorganisms and in the acute inflammatory response. However, their role in colitis and colitis-associated colorectal cancer is still under debate. This study aims to dissect the role of neutrophils in these pathologic contexts by using a rigorous genetic approach. Neutrophil-deficient mice (Csf3r-/- mice) were used in classic models of colitis and colitis-associated colorectal cancer and the role of neutrophils was assessed by histologic, cellular, and molecular analyses coupled with adoptive cell transfer. We also performed correlative analyses using human datasets. Csf3r-/- mice showed increased susceptibility to colitis and colitis-associated colorectal cancer compared with control Csf3r+/+ mice and adoptive transfer of neutrophils in Csf3r-/- mice reverted the phenotype. In colitis, Csf3r-/- mice showed increased bacterial invasion and a reduced number of healing ulcers in the colon, indicating a compromised regenerative capacity of epithelial cells. Neutrophils were essential for γδ T-cell polarization and IL22 production. In patients with ulcerative colitis, expression of CSF3R was positively correlated with IL22 and IL23 expression. Moreover, gene signatures associated with epithelial-cell development, proliferation, and antimicrobial response were enriched in CSF3Rhigh patients. Our data support a model where neutrophils mediate protection against intestinal inflammation and colitis-associated colorectal cancer by controlling the intestinal microbiota and driving the activation of an IL22-dependent tissue repair pathway. 

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Related works

Is supplemented by
Publication: 38349973 (PMID)