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Determining Th17 lineage commitment
Author(s) -
Stritesky Gretta Lynne,
Yeh Norman,
Mathur Anubhav,
Kaplan Mark
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.846.24
Subject(s) - interleukin 17 , phenotype , rar related orphan receptor gamma , stimulation , secretion , interleukin 23 , immunology , microbiology and biotechnology , interleukin 12 , biology , in vitro , cytotoxic t cell , cytokine , immune system , endocrinology , gene , genetics , foxp3
Autoimmune diseases including type 1 diabetes, multiple sclerosis, and rheumatoid arthritis are thought to be diseases mediated by a newly characterized subset of CD4+ T cells, Th17 cells. Th17 cells develop in the presence of TGFβ+IL‐6, and IL‐23 is thought to play a role in maintaining the phenotype. However, the commitment of Th17 cells is still unclear. We show that Th17 cells cultured with antigen presenting cells for multiple rounds of stimulation secrete high levels of IL‐17 upon re‐stimulation. IL‐17 production in long term cultures is enhanced when Th17 cells are cultured with IL‐1β. We further show that Th17 cells are not committed to secrete IL‐17. After three rounds of stimulation Th17 cells cultured with cytokines that promote Th1 or Th2 development have decreased levels of IL‐17 and increased levels in IFN‐γ and IL‐4, respectively. Decreased IL‐17 in Th17 cells cultured in opposing cytokines correlates with a decrease in mRNA expression of Th17 specific factors including RORγt and IL‐23R. This is in contrast to the ability of Th1 and Th2 cells to maintain their phenotype under these culture conditions. Thus, our results suggest that Th17 cells are not committed to an IL‐17‐secreting phenotype.