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Reciprocal effects of IFN‐β and IL‐12 on STAT4 activation and cytokine induction in T cells
Author(s) -
Fahey Angela J.,
Robins R. Adrian,
Constantinescu Cris S.
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1006633
Subject(s) - cytokine , biology , stat4 , immunology , cytokine receptor , interleukin 10 , signal transduction , interferon , microbiology and biotechnology , receptor , stat , cancer research , genetics , stat3
IL‐12 is an immunoregulatory cytokine, which promotes Th1 cell differentiation and is a major inducer of IFN‐γ. IFN‐β, a Type I IFN used in the treatment of multiple sclerosis, has been shown to significantly increase the expression of the anti‐inflammatory cytokine IL‐10, a major suppressor of Th1 cytokines. The beneficial immunomodulatory effects of IFN‐β may in part be a result of its ability to suppress IL‐12. However, IL‐12 and IFN‐β signal via the STAT4 pathway. Our aim was to investigate the relationship between IL‐12 and IFN‐β by observing the effect of prior exposure to IL‐12 or IFN‐β on the ability of T cells to subsequently respond to the other cytokine. We report that IFN‐β increases IL‐12‐induced STAT4 phosphorylation and up‐regulates IL‐12 receptor β1 and β2 expression. However, despite this up‐regulation, IFN‐β suppressed IL‐12‐induced IFN‐γ expression. Our results suggest that this may be a result of the parallel induction of IL‐10 by IFN‐β.