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  • Title: CD161 is a marker of all human IL-17-producing T-cell subsets and is induced by RORC.
    Author: Maggi L, Santarlasci V, Capone M, Peired A, Frosali F, Crome SQ, Querci V, Fambrini M, Liotta F, Levings MK, Maggi E, Cosmi L, Romagnani S, Annunziato F.
    Journal: Eur J Immunol; 2010 Aug; 40(8):2174-81. PubMed ID: 20486123.
    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 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.
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