title: Th17 cells are long lived and retain a stem cell-like molecular signature.
abstract: Th17 cells have been described as short lived, but this view is at odds with their capacity to trigger protracted damage to normal and transformed tissues. We report that Th17 cells, despite displaying low expression of CD27 and other phenotypic markers of terminal differentiation, efficiently eradicated tumors and caused autoimmunity, were long lived, and maintained a core molecular signature resembling early memory CD8(+) cells with stem cell-like properties. In addition, we found that Th17 cells had high expression of Tcf7, a direct target of the Wnt and β-catenin signaling axis, and accumulated β-catenin, a feature observed in stem cells. In vivo, Th17 cells gave rise to Th1-like effector cell progeny and also self-renewed and persisted as IL-17A-secreting cells. Multipotency was required for Th17 cell-mediated tumor eradication because effector cells deficient in IFN-γ or IL-17A had impaired activity. Thus, Th17 cells are not always short lived and are a less-differentiated subset capable of superior persistence and functionality.
authors.affiliation: National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Muranski
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Borman
authors.forename: Sid P
authors.initials: SP
authors.lastname: Kerkar
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Klebanoff
authors.forename: Yun
authors.initials: Y
authors.lastname: Ji
authors.forename: Luis
authors.initials: L
authors.lastname: Sanchez-Perez
authors.forename: Madhusudhanan
authors.initials: M
authors.lastname: Sukumar
authors.forename: Robert N
authors.initials: RN
authors.lastname: Reger
authors.forename: Zhiya
authors.initials: Z
authors.lastname: Yu
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kern
authors.forename: Rahul
authors.initials: R
authors.lastname: Roychoudhuri
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Ferreyra
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.forename: Scott K
authors.initials: SK
authors.lastname: Durum
authors.forename: Lionel
authors.initials: L
authors.lastname: Feigenbaum
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Palmer
authors.forename: Paul A
authors.initials: PA
authors.lastname: Antony
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Arian
authors.initials: A
authors.lastname: Laurence
authors.forename: Robert L
authors.initials: RL
authors.lastname: Danner
authors.forename: Luca
authors.initials: L
authors.lastname: Gattinoni
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics; D020869:Gene Expression Profiling; D020381:Interleukin-17 / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7