title: IL-17 mediated inflammation promotes tumor growth and progression in the skin.
abstract: The mechanism for inflammation associated tumor development is a central issue for tumor biology and immunology and remains to be fully elucidated. Although IL-17 is implicated in association with inflammation mediated carcinogenesis, mechanisms are largely elusive. In the current studies, we showed that IL-17 receptor-A gene deficient (IL-17R-/-) mice were resistant to chemical carcinogen-induced cutaneous carcinogenesis, a well-established inflammation associated tumor model in the skin. The deficiency in IL-17R increased the infiltration of CD8+ T cells whereas it inhibited the infiltration of CD11b+ myeloid cells and development of myeloid derived suppressor cells. Inflammation induced skin hyperplasia and production of pro-tumor inflammatory molecules were inhibited in IL-17R-/- mice. We found that pre-existing inflammation in the skin increased the susceptibility to tumor growth, which was associated with increased development of tumor specific IL-17 producing T cells. This inflammation induced susceptibility to tumor growth was abrogated in IL-17R-/- mice. Finally, neutralizing IL-17 in mice that had already developed chemical carcinogen induced skin tumors could inhibit inflammation mediated tumor progression at late stages. These results demonstrate that IL-17 mediated inflammation is an important mechanism for inflammation mediated promotion of tumor development. The study has major implications for targeting IL-17 in prevention and treatment of tumors.
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Donggou
authors.initials: D
authors.lastname: He
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Nabiha
authors.initials: N
authors.lastname: Yusuf
authors.forename: Craig A
authors.initials: CA
authors.lastname: Elmets
authors.forename: Mohammad
authors.initials: M
authors.lastname: Athar
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Katiyar
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes; D002465:Cell Movement; D018450:Disease Progression; D004198:Disease Susceptibility; D007249:Inflammation / Q000150:complications; D020381:Interleukin-17 / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000276:immunology*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology
chemical_list: D020381:Interleukin-17; D053722:Receptors, Interleukin-17