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dc.contributor.authorAmeri, Amir H.
dc.date.accessioned2019-05-07T09:18:36Z
dc.date.created2019-05
dc.date.issued2019-05-06
dc.date.submitted2019
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:39712821*
dc.description.abstractChronic inflammation’s tumor-promoting potential is well-recognized; however, the mechanism underlying the development of this immune environment is unknown. In contrast to anti-tumor immunity in acute allergic contact dermatitis (ACD), chronic ACD is marked by a type 2 tumor-promoting immune environment. The opposite effects of chronic versus acute ACD on cancer enabled a unique paradigm to investigate how a tumor-promoting chronic inflammation develops in the first place. Epidermis-derived IL-33 upregulation and its induction of T regulatory cell 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 ACD-induced skin cancer compared to wild-type controls (p = 0.0002). IL-33’s direct signaling onto T regulatory cells was required for the development of a cancer-promoting immune environment in the skin. Notably, IL-33 to Treg signaling was also required for colorectal cancer development in colitis model (p < 0.0001). Significantly increased IL-33 and Treg marked the cancer-prone chronic inflammatory diseases of skin and colon in humans. Our findings elucidate the role of IL-33/Treg axis in the creation of tumor-promoting immune environment in chronic inflammatory diseases, which provide therapeutic targets for cancer prevention and treatment in the high-risk patients.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dash.licenseLAA
dc.titleIL-33/Regulatory T Cell Axis Triggers the Development of a Tumor-Promoting Immune Environment in Chronic Inflammation
dc.typeThesis or Dissertation
dash.depositing.authorAmeri, Amir H.
dc.date.available2019-05-07T09:18:36Z
thesis.degree.date2019
thesis.degree.grantorHarvard Medical School
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Medicine
dash.workflow.commentsOSC obscured DAC signature (cbl 2019)
dc.type.materialtext
dash.identifier.vireohttp://etds.lib.harvard.edu/hms/admin/view/895
dc.description.keywordschronic inflammation; carcinogenesis; regulatory T cell; IL-33; inflammatory bowel disease
dash.author.emailamirameri7@gmail.com


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