Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 7, Pages 2646-2651Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1815016116
Keywords
interleukin (IL)-33; regulatory T cells; chronic inflammation; cancer promotion; allergic contact dermatitis
Categories
Funding
- Mucosal Immunology Studies Team (MIST) [U01, RFA-AI-15-023]
- Burroughs Wellcome Fund
- Howard Hughes Medical Institute
- Sidney Kimmel Foundation
- Cancer Research Institute
- NIH [K08AR068619, DP5OD021353]
Ask authors/readers for more resources
Chronic inflammation's tumor-promoting potential is well-recognized; however, the mechanism underlying the development of this immune environment is unknown. Studying the transition from acute, tumor-suppressive to chronic, tumor-promoting allergic contact dermatitis (ACD) revealed how tumor-promoting chronic inflammation develops. Epidermis-derived interleukin (IL)-33 up-regulation and its induction of regulatory T cell (Treg) accumulation in the skin preceded the transition from acute to chronic ACD and triggered the tumor-promoting immune environment in chronic ACD. Mice lacking IL-33 were protected from chronic ACD and its skin cancer sequela compared with wild-type controls (P = 0.0002). IL-33's direct signaling onto Tregs was required for the development of the tumor-promoting immune environment in the skin. IL-33-Treg signaling was also required for chronic colitis and its associated colorectal cancer development in a colitis model (P < 0.0001). Significantly increased IL-33 and Tregs marked the perilesional skin and colon in patients with cancer-prone chronic inflammatory diseases. Our findings elucidate the role of the IL-33/Treg axis in creating a tumor-promoting immune environment in chronic inflammatory diseases and suggest therapeutic targets for cancer prevention and treatment in high-risk patients.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available