title: 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 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.
authors.affiliation: Centre of Excellence DENOThe, University of Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Maggi
authors.forename: Veronica
authors.initials: V
authors.lastname: Santarlasci
authors.forename: Manuela
authors.initials: M
authors.lastname: Capone
authors.forename: Anna
authors.initials: A
authors.lastname: Peired
authors.forename: Francesca
authors.initials: F
authors.lastname: Frosali
authors.forename: Sarah Q
authors.initials: SQ
authors.lastname: Crome
authors.forename: Valentina
authors.initials: V
authors.lastname: Querci
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Fambrini
authors.forename: Francesco
authors.initials: F
authors.lastname: Liotta
authors.forename: Megan K
authors.initials: MK
authors.lastname: Levings
authors.forename: Enrico
authors.initials: E
authors.lastname: Maggi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cosmi
authors.forename: Sergio
authors.initials: S
authors.lastname: Romagnani
authors.forename: Francesco
authors.initials: F
authors.lastname: Annunziato
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000235:genetics / Q000378:metabolism*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D019076:Transgenes
chemical_list: D015415:Biomarkers; D015704:CD4 Antigens; D016827:CD8 Antigens; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D055651:NK Cell Lectin-Like Receptor Subfamily B; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta