Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages

Laurie E. Harrington, Robin D. Hatton, Paul R. Mangan, Henrietta Turner, Theresa L. Murphy, Kenneth M. Murphy, Casey T. Weaver

Research output: Contribution to journalArticlepeer-review

3764 Scopus citations

Abstract

CD4+ T cells producing interleukin 17 (IL-17) are associated with autoimmunity, although the precise mechanisms that control their development are undefined. Here we present data that challenge the idea of a shared developmental pathway with T helper type 1 (TH1) or TH2 lineages and instead favor the idea of a distinct effector lineage we call 'TH. The development of TH-17 cells from naive precursor cells was potently inhibited by interferon-γ (IFN-γ) and IL-4, whereas committed TH-17 cells were resistant to suppression by TH1 or TH2 cytokines. In the absence of IFN-γ and IL-4, IL-23 induced naive precursor cells to differentiate into TH-17 cells independently of the transcription factors STAT1, T-bet, STAT4 and STAT6. These findings provide a basis for understanding how inhibition of IFN-γ signaling enhances development of pathogenic TH-17 effector cells that can exacerbate autoimmunity.

Original languageEnglish
Pages (from-to)1123-1132
Number of pages10
JournalNature immunology
Volume6
Issue number11
DOIs
StatePublished - Nov 2005

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