STAT-3-independent production of IL-17 by mouse innate-like αβ T cells controls ocular infection

J Exp Med. 2018 Apr 2;215(4):1079-1090. doi: 10.1084/jem.20170369. Epub 2018 Feb 28.


Appropriate regulation of IL-17 production in the host can mean the difference between effective control of pathogens and uncontrolled inflammation that causes tissue damage. Investigation of conventional CD4+ T cells (Th17 cells) has yielded invaluable insights into IL-17 function and its regulation. More recently, we and others reported production of IL-17 from innate αβ+ T cell populations, which was shown to occur primarily via IL-23R signaling through the transcription factor STAT-3. In our current study, we identify promyelocytic leukemia zinc finger (PLZF)-expressing iNKT, CD4-/CD8+, and CD4-/CD8- (DN) αβ+T cells, which produce IL-17 in response to TCR and IL-1 receptor ligation independently of STAT-3 signaling. Notably, this noncanonical pathway of IL-17 production may be important in mucosal defense and is by itself sufficient to control pathogenic Staphylococcus aureus infection at the ocular surface.

Publication types

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

MeSH terms

  • Animals
  • Eye Infections / immunology*
  • Eye Infections / pathology*
  • Immunity, Innate*
  • Immunologic Memory
  • Interleukin-17 / biosynthesis*
  • Interleukins / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mucous Membrane / immunology
  • Mucous Membrane / microbiology
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Phosphorylation
  • Promyelocytic Leukemia Zinc Finger Protein / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Staphylococcus aureus / physiology
  • T-Lymphocytes / metabolism
  • Th17 Cells / metabolism
  • Thymus Gland / metabolism


  • Interleukin-17
  • Interleukins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Promyelocytic Leukemia Zinc Finger Protein
  • Receptors, Antigen, T-Cell, alpha-beta
  • STAT3 Transcription Factor
  • Zbtb16 protein, mouse