CD161 is a marker of all human IL-17-producing T-cell subsets and is induced by RORC

Eur J Immunol. 2010 Aug;40(8):2174-81. doi: 10.1002/eji.200940257.


We have previously shown that human Th17 lymphocytes are characterized by the selective expression of IL-23 receptor (IL-23R), CCR6, CD161, and the transcription factor retinoic acid-related orphan receptor C (RORC), and originate from a CD161(+)CD4(+) naïve T-cell precursor in response to the combined activity of IL-1β and IL-23. We show here that not only CD4(+)TCRαβ(+), but also CD8(+)TCRαβ(+), CD4(-)CD8(-) TCRαβ(+), and CD4(-)CD8(-) TCRγδ(+) circulating lymphocytes that produce IL-17 express the distinctive marker CD161 on their surface. In addition, we demonstrate that CD161 expression identifies CD8(+) and CD4(-)CD8(-) umbilical cord blood T cells that already express RORC and IL-23R mRNA and that can be induced to differentiate into IL-17-producing cells in the presence of IL-1β and IL-23. Finally, we provide evidence that umbilical cord blood naïve CD4(+)CD161(-) T cells, upon lentivirus-mediated transduction with RORC2 can acquire the ability to express IL-23R, IL-1RI, and CD161, as well as to produce IL-17. Taken together, these data allow to conclude that T-cell subsets able to produce IL-17, as well as precursors of IL-17-producing T cells, exhibit surface expression of CD161, and that this feature is at least in part RORC2-dependent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism*
  • CD4 Antigens / biosynthesis
  • CD8 Antigens / biosynthesis
  • Cell Differentiation
  • Cells, Cultured
  • Humans
  • Interleukin-17 / metabolism
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism
  • Interleukin-23 / immunology
  • Interleukin-23 / metabolism
  • Lymphocyte Activation
  • NK Cell Lectin-Like Receptor Subfamily B / genetics
  • NK Cell Lectin-Like Receptor Subfamily B / metabolism*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Transgenes


  • Biomarkers
  • CD4 Antigens
  • CD8 Antigens
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-23
  • NK Cell Lectin-Like Receptor Subfamily B
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta