Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
- PMID: 16200070
- DOI: 10.1038/ni1254
Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
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.
Comment in
-
T(H)-17: a giant step from T(H)1 and T(H)2.Nat Immunol. 2005 Nov;6(11):1069-70. doi: 10.1038/ni1105-1069. Nat Immunol. 2005. PMID: 16239919 No abstract available.
Similar articles
-
T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cells.Nat Immunol. 2002 Jun;3(6):549-57. doi: 10.1038/ni794. Epub 2002 May 13. Nat Immunol. 2002. PMID: 12006974
-
Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells.J Exp Med. 1997 Mar 3;185(5):817-24. doi: 10.1084/jem.185.5.817. J Exp Med. 1997. PMID: 9120387 Free PMC article.
-
Transforming growth factor-beta induces development of the T(H)17 lineage.Nature. 2006 May 11;441(7090):231-4. doi: 10.1038/nature04754. Epub 2006 Apr 30. Nature. 2006. PMID: 16648837
-
Stat4- and Stat6-deficient mice as models for manipulating T helper cell responses.Biochem Soc Trans. 1997 May;25(2):359-60. doi: 10.1042/bst0250359. Biochem Soc Trans. 1997. PMID: 9191117 Review. No abstract available.
-
T helper differentiation proceeds through Stat1-dependent, Stat4-dependent and Stat4-independent phases.Curr Top Microbiol Immunol. 1999;238:13-26. doi: 10.1007/978-3-662-09709-0_2. Curr Top Microbiol Immunol. 1999. PMID: 10087648 Review.
Cited by
-
Eutopic and Ectopic Endometrial Interleukin-17 and Interleukin-17 Receptor Expression at the Endometrial-Myometrial Interface in Women with Adenomyosis: Possible Pathophysiology Implications.Int J Mol Sci. 2024 Oct 17;25(20):11155. doi: 10.3390/ijms252011155. Int J Mol Sci. 2024. PMID: 39456936 Free PMC article.
-
Immune and inflammatory role in renal disease.Compr Physiol. 2013 Apr;3(2):957-76. doi: 10.1002/cphy.c120028. Compr Physiol. 2013. PMID: 23720336 Free PMC article. Review.
-
IL-17A in human respiratory diseases: innate or adaptive immunity? Clinical implications.Clin Dev Immunol. 2013;2013:840315. doi: 10.1155/2013/840315. Epub 2013 Jan 17. Clin Dev Immunol. 2013. PMID: 23401702 Free PMC article. Review.
-
A T cell extrinsic mechanism by which IL-2 dampens Th17 differentiation.J Autoimmun. 2015 May;59:38-42. doi: 10.1016/j.jaut.2015.02.001. Epub 2015 Feb 26. J Autoimmun. 2015. PMID: 25725581 Free PMC article.
-
Inhibitory effect of IL-17 on neural stem cell proliferation and neural cell differentiation.BMC Immunol. 2013 Apr 23;14:20. doi: 10.1186/1471-2172-14-20. BMC Immunol. 2013. PMID: 23617463 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous