Batf-dependent Th17 cells critically regulate IL-23 driven colitis-associated colon cancer.

Area of Science:

• Immunology
• Oncology
• Gastroenterology

Background:

• Inflammatory bowel diseases (IBD) increase the risk of colorectal cancer (CRC).
• Th17 cells and associated transcription factors play a role in cancer development.
• Understanding the role of transcription factors like Batf in CRC is crucial.

Purpose of the Study:

• To investigate the functional role of Th17-associated transcription factors in sporadic and colitis-associated colon cancer.
• To evaluate the role of Batf (basic leucine zipper transcription factor ATF-like) in colon carcinogenesis using mouse models.
• To examine Batf and RORγt expression in human IBD and CRC tissues.

Main Methods:

• Utilized mice deficient or transgenic for Batf to study Th17 cell involvement in colon carcinogenesis.
• Analyzed Batf and RORγt expression in human ulcerative colitis (UC), Crohn's disease (CD), and CRC samples.
• Assessed the coexpression of Batf with key cytokines (IL-23, IL-23R, IL-17a, IL-6) in tumor-infiltrating CD4+ T cells.

Main Results:

• Batf expression, but not RORγt, was significantly increased in UC and CRC tissues, correlating with IL-23 and IL-23R expression.
• Batf was coexpressed with IL-17a, IL-23R, and IL-6 within CRC-infiltrating CD4+ T cells.
• Batf-deficient mice showed reduced inflammation-induced and sporadic colon tumors, with altered T cell profiles and cytokine levels.

Conclusions:

• Batf-dependent IL-23R+IL-6+CD4+ Th17 cells are critical regulators of IL-23-driven colitis-associated tumor formation and sporadic colon tumor progression.
• Batf-dependent T cells are crucial for CRC development.
• Targeting Batf-dependent IL-23R+ T cells represents a potential therapeutic strategy to limit CRC progression.