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

Abstract 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 CD161CD4 naıve T-cell precursor in response to the combined activity of IL-1b and IL-23. We show here that not only CD4TCRab, but also CD8TCRab, CD4CD8 TCRab, and CD4CD8 TCRgd circulating lymphocytes that produce IL-17 express the distinctive marker CD161 on their surface. In addition, we demonstrate that CD161 expression identifies CD8 and CD4CD8 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-1b and IL-23. Finally, we provide evidence that umbilical cord blood naıve CD4CD161 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.