Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions

Sci Adv. 2023 Oct 27;9(43):eadg6874. doi: 10.1126/sciadv.adg6874. Epub 2023 Oct 25.

Abstract

Interleukins are secreted proteins that regulate immune responses. Among these, the interleukin 12 (IL-12) family holds a central position in inflammatory and infectious diseases. Each family member consists of an α and a β subunit that together form a composite cytokine. Within the IL-12 family, IL-35 remains particularly ill-characterized on a molecular level despite its key role in autoimmune diseases and cancer. Here we show that both IL-35 subunits, IL-12α and EBI3, mutually promote their secretion from cells but are not necessarily secreted as a heterodimer. Our data demonstrate that IL-12α and EBI3 are stable proteins in isolation that act as anti-inflammatory molecules. Both reduce secretion of proinflammatory cytokines and induce the development of regulatory T cells. Together, our study reveals IL-12α and EBI3, the subunits of IL-35, to be functionally active anti-inflammatory immune molecules on their own. This extends our understanding of the human cytokine repertoire as a basis for immunotherapeutic approaches.

MeSH terms

  • Cytokines / metabolism
  • Humans
  • Interleukin-12* / metabolism
  • Interleukins* / metabolism
  • Minor Histocompatibility Antigens / metabolism
  • T-Lymphocytes, Regulatory

Substances

  • Cytokines
  • EBI3 protein, human
  • Interleukin-12
  • Interleukins
  • Minor Histocompatibility Antigens