Nuclear factor-κB-dependent reversal of aging-induced alterations in T cell cytokines

Mei Chuan Huang, Jia Jun Liao, Stephen Bonasera, Dan L. Longo, Edward J. Goetzl

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Immunosenescence is characterized by decreases in protective immune responses and increases in inflammation and autoimmunity. The T helper (Th)17 subset of cluster-of-differentiation (CD)4 T cells, which is identified by its generation of interleukin (IL) -17, is implicated in autoimmune pathogenesis. To elucidate immunosenescent changes in Th17 cell cytokines, splenic CD4 T cells from 22- to 24-month-old (old) mice and 6- to 10-wk-old (young) mice were incubated on anti-CD3 plus anti-CD28 (anti-T cell antigen receptor) antibodies. After 96 h, T cells of old C57BL/6 and CBA mice generated up to 20-fold more IL-17 and up to 3-fold more IL-6 than those of young mice; T cells of young mice generated up to 5-fold more IL-21 than those of old mice; and no difference was found for IFN-γ. At 24 h, cytokine mRNA levels paralleled 96 h cytokine concentrations. Naive CD4 T cells from old mice incubated on anti-T cell antigen receptor antibodies with transforming growth factor-γ, IL-1, IL-6, and IL-23 to induce de novo differentiation of Th17 cells had more IL-17 mRNA and produced more IL-17 than those of young mice. BAY11-7082 and the phytochemicals triptolide and butein suppressed nuclear concentrations of nuclear factor-κB and secreted levels of IL-17, IL-21, and IFN-γ in parallel, with greater potency in Th17 cells from young than old mice. Pharmacological correction of altered generation of Th17 cell cytokines in immunosenescence represents a novel therapeutic approach to aging-induced inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)2142-2150
Number of pages9
JournalFASEB Journal
Volume22
Issue number7
DOIs
StatePublished - Jul 2008

Keywords

  • Autoimmunity
  • Immunosenescence
  • Inflammation
  • Phytochemicals

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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