Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12

Immunity. 2000 Nov;13(5):715-25. doi: 10.1016/s1074-7613(00)00070-4.

Abstract

A novel sequence discovered in a computational screen appears distantly related to the p35 subunit of IL-12. This factor, which we term p19, shows no biological activity by itself; instead, it combines with the p40 subunit of IL-12 to form a novel, biologically active, composite cytokine, which we term IL-23. Activated dendritic cells secrete detectable levels of this complex. IL-23 binds to IL-12R beta 1 but fails to engage IL-12R beta 2; nonetheless, IL-23 activates Stat4 in PHA blast T cells. IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low)) T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population. Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Cytokines / genetics*
  • Cytokines / immunology
  • Databases, Factual
  • Humans
  • Interleukin-12 / genetics*
  • Interleukin-12 / immunology
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins / genetics*
  • Interleukins / immunology
  • Mice
  • Molecular Sequence Data
  • Sequence Alignment
  • Sequence Analysis

Substances

  • Cytokines
  • IL23A protein, human
  • Il23a protein, mouse
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins
  • Interleukin-12

Associated data

  • GENBANK/AF301619
  • GENBANK/AF301620