Nature Immunology 6, 1123 - 1132 (2005)
Published online: 2 October 2005; | doi:10.1038/ni1254
Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineagesLaurie E Harrington1, Robin D Hatton1, Paul R Mangan1, Henrietta Turner1, Theresa L Murphy2, Kenneth M Murphy2
& Casey T Weaver11
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. 2
Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Correspondence should be addressed to Casey T Weaver weaver@path.uab.edu 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-17'. The development of TH-17 cells from naive precursor cells was potently inhibited by interferon- (IFN-) and IL-4, whereas committed TH-17 cells were resistant to suppression by TH1 or TH2 cytokines. In the absence of IFN- 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- signaling enhances development of pathogenic TH-17 effector cells that can exacerbate autoimmunity.
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