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Interleukins 1 and 23 are critical for human Th17 differentiation
Author(s) -
Liu Hong,
RohowskyKochan Christine
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.22.2_supplement.435
Subject(s) - rar related orphan receptor gamma , cd28 , il 2 receptor , microbiology and biotechnology , interleukin 17 , chemistry , cytokine , interleukin , cd3 , population , interleukin 4 , biology , immunology , endocrinology , t cell , medicine , foxp3 , immune system , cd8 , environmental health
Objective: To determine the critical factors involved in the differentiation of human naïve T cells into IL‐17 producing cells and the role of IL‐27 in this process. Methods: Naïve CD4 + CD45RA + T cells were purified from peripheral blood of healthy donors by using magnetic beads. Cells were stimulated with CD3 and CD28 antibody, in the presence and absence of IL‐1β, IL‐23, IL‐6, TGF‐β for 6 days. Duplicate cultures received various doses of IL‐27. IL‐17 and IFNγ levels were measured by ELISA and intracellular cytokine staining. IL‐17 and RORC mRNA expression was detected by real time PCR. Results: The naive T cell population was phenotypically characterized as being CD4 + CD45RA + CD25 − CCR7 + CD11a + . Crosslinking CD3 and CD28 on these naïve T cells resulted in very low levels of IL‐17. Addition of IL‐1β together with IL‐23 markedly increased IL‐17 production and IL‐17 and RORC mRNA expression as did the combination of IL‐1β, IL‐6 and IL‐23. IL‐6 and TGF‐β did not significantly promote IL‐17 secretion. A dose dependent inhibition of the IL‐1β/IL‐23‐induced Il‐17 response was observed in the presence of IFNγ. The mechanism by which IL‐1β/IL‐23 promotes IL‐17 secretion and the effect of IL‐27 is under investigation. Conclusions: IL‐1β and IL‐23 are critical factors promoting the differentiation of human naïve T cells into IL‐17 producing cells.