A novel IL-23p19/Ebi3 (IL-39) cytokine mediates inflammation in Lupus-like mice

Eur J Immunol. 2016 Jun;46(6):1343-50. doi: 10.1002/eji.201546095. Epub 2016 Apr 13.


Interleukin-12 family cytokines have emerged as critical regulators of immunity with some members (IL-12, IL-23) associated with disease pathogenesis while others (IL-27, IL-35) mitigate autoimmune diseases. Each IL-12 family member is comprised of an α and a β chain, and chain-sharing is a key feature. Although four bona fide members have thus far been described, promiscuous chain-pairing between alpha (IL-23p19, IL-27p28, IL-12/IL-35p35) and beta (IL-12/IL-23p40, IL-27/IL-35Ebi3) subunits, predicts six possible heterodimeric IL-12 family cytokines. Here, we describe a new IL-12 member composed of IL-23p19 and Ebi3 heterodimer (IL-39) that is secreted by LPS-stimulated B cells and GL7(+) activated B cells of lupus-like mice. We further show that IL-39 mediates inflammatory responses through activation of STAT1/STAT3 in lupus-like mice. Taken together, our results show that IL-39 might contribute to immunopathogenic mechanisms of systemic lupus erythematosus, and could be used as a possible target for its treatment.

Keywords: Autoimmunity ⋅ IL-12 ⋅ IL-23p19 ⋅ IL-27/IL-35Ebi3 ⋅ IL-39 ⋅ Inflammation ⋅ Systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Immunophenotyping
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interleukin-23 Subunit p19 / chemistry
  • Interleukin-23 Subunit p19 / genetics
  • Interleukin-23 Subunit p19 / metabolism*
  • Lupus Erythematosus, Systemic / etiology*
  • Lupus Erythematosus, Systemic / metabolism*
  • Lupus Erythematosus, Systemic / pathology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred MRL lpr
  • Minor Histocompatibility Antigens / chemistry
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / metabolism*
  • Protein Multimerization
  • Receptors, Cytokine / chemistry
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism*
  • Receptors, Interleukin / metabolism
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction


  • Ebi3 protein, mouse
  • Interleukin-23 Subunit p19
  • Minor Histocompatibility Antigens
  • Receptors, Cytokine
  • Receptors, Interleukin
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • interleukin-23 receptor, mouse