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Th17 Cells Are Long Lived and Retain a Stem Cell-like Molecular Signature

  1. Author:
    Muranski, P.
    Borman, Z. A.
    Kerkar, S. P.
    Klebanoff, C. A.
    Ji, Y.
    Sanchez-Perez, L.
    Sukumar, M.
    Reger, R. N.
    Yu, Z. Y.
    Kern, S. J.
    Roychoudhuri, R.
    Ferreyra, G. A.
    Shen, W.
    Durum, S. K.
    Feigenbaum, L.
    Palmer, D. C.
    Antony, P. A.
    Chan, C. C.
    Laurence, A.
    Danner, R. L.
    Gattinoni, L.
    Restifol, N. P.

  2. Author Address

    [Muranski, Pawel; Borman, Zachary A.; Kerkar, Sid P.; Klebanoff, Christopher A.; Ji, Yun; Sanchez-Perez, Luis; Sukumar, Madhusudhanan; Reger, Robert N.; Yu, Zhiya; Roychoudhuri, Rahul; Palmer, Douglas C.; Gattinoni, Luca; Restifol, Nicholas P.] NCI, Bethesda, MD 20892 USA. [Kern, Steven J.; Ferreyra, Gabriela A.; Danner, Robert L.] NIH, Ctr Clin, Dept Crit Care Med, Funct Genom & Prote Facil, Bethesda, MD 20892 USA. [Shen, Wei; Durum, Scott K.] NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. [Feigenbaum, Lionel] Sci Applicat Int Corp SAIC, NCI, Frederick, MD 21702 USA. [Antony, Paul A.] Univ Maryland, Sch Med, Dept Pathol, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Antony, Paul A.] Univ Maryland, Sch Med, Tumor Immunol & lmmunotherapy Program, Baltimore, MD 21201 USA. [Chan, Chi-Chao] NEI, NIH, Bethesda, MD 20892 USA. [Laurence, Arian] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.;Restifol, NP (reprint author), NCI, CRC10 Room 3W5816, Bethesda, MD 20892 USA;restifon@mail.nih.gov
    1. Year: 2011
    2. Date: Dec
  2. Journal: Immunity
    1. 35
    2. 6
    3. Pages: 972-985
  4. Type of Article: Article
  5. ISSN: 1074-7613
  1. 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 beta-catenin signaling axis, and accumulated beta-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-gamma 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.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.immuni.2011.09.019
  3. View record in Web of Science®
  4. WOS: 000298777300015

Library Notes

  1. Fiscal Year: FY2011-2012
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