The Immunobiology of the Interleukin-12 Family: Room for Discovery

Immunity. 2019 Apr 16;50(4):851-870. doi: 10.1016/j.immuni.2019.03.011.

Abstract

The discovery of interleukin (IL)-6 and its receptor subunits provided a foundation to understand the biology of a group of related cytokines: IL-12, IL-23, and IL-27. These family members utilize shared receptors and cytokine subunits and influence the outcome of cancer, infection, and inflammatory diseases. Consequently, many facets of their biology are being therapeutically targeted. Here, we review the landmark discoveries in this field, the combinatorial biology inherent to this family, and how patient datasets have underscored the critical role of these pathways in human disease. We present significant knowledge gaps, including how similar signals from these cytokines can mediate distinct outcomes, and discuss how a better understanding of the biology of the IL-12 family provides new therapeutic opportunities.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / therapy
  • Cytokines / antagonists & inhibitors
  • Cytokines / genetics
  • Cytokines / immunology*
  • Humans
  • Immunity, Cellular
  • Inflammation / immunology
  • Interleukin-12 / antagonists & inhibitors
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology*
  • Interleukin-27 / therapeutic use
  • Lymphocyte Subsets / immunology
  • Lymphopoiesis
  • Mice
  • Mice, Knockout
  • Multigene Family / genetics
  • Multigene Family / immunology*
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy
  • Protein Subunits
  • Structure-Activity Relationship

Substances

  • Cytokines
  • Interleukin-27
  • Protein Subunits
  • Interleukin-12