Ameri AH, Moradi Tuchayi S, Zaalberg A, Park JH, Ngo KH, Li T, Lopez E, Colonna M, Lee RT, Mino-Kenudson M, Demehri S. 2019. IL-33/regulatory T cell axis triggers the development of a tumor-promoting immune environment in chronic inflammation. Proceedings of the National Academy of Sciences of the United States of America. 116(7):2646-2651. Pubmed: 30696763 DOI:10.1073/pnas.1815016116


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 ( = 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 ( < 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.

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Rich Lee seeks to understand heart failure and metabolic diseases that accompany human aging, and translate that understanding into therapies. Lee is an active clinician, regularly treating patients at Brigham and Women’s Hospital.

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