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 (T(H)1) or T(H)2 lineages and instead favor the idea of a distinct effector lineage we call 'T(H)-17'. The development of T(H)-17 cells from naive precursor cells was potently inhibited by interferon-gamma (IFN-gamma) and IL-4, whereas committed T(H)-17 cells were resistant to suppression by T(H)1 or T(H)2 cytokines. In the absence of IFN-gamma and IL-4, IL-23 induced naive precursor cells to differentiate into T(H)-17 cells independently of the transcription factors STAT1, T-bet, STAT4 and STAT6. These findings provide a basis for understanding how inhibition of IFN-gamma signaling enhances development of pathogenic T(H)-17 effector cells that can exacerbate autoimmunity.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Harrington LE,Hatton RD,Mangan PR,Turner H,Murphy TL,Murphy KM,Weaver CTdoi
10.1038/ni1254keywords:
subject
Has Abstractpub_date
2005-11-01 00:00:00pages
1123-32issue
11eissn
1529-2908issn
1529-2916pii
ni1254journal_volume
6pub_type
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