Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor.
We demonstrate that CD161 is a highly up-regulated gene in human interleukin (IL) 17 T helper cell (Th17) clones and that all IL-17-producing cells are contained in the CD161(+) fraction of CD4(+) T cells present in the circulation or in inflamed tissues, although they are not CD1-restricted natural killer T cells. More importantly, we show that all IL-17-producing cells originate from CD161(+) naive CD4(+) T cells of umbilical cord blood, as well as of the postnatal thymus, in response to the combined activity of IL-1 beta and IL-23. These findings implicate CD161 as a novel surface marker for human Th17 cells and demonstrate the exclusive origin of these cells from a CD161(+)CD4(+) T cell progenitor.
Cosmi
Lorenzo
L
Department of Internal Medicine and DENOTHE Center, University of Florence, Florence 50134, Italy.
De Palma
Raffaele
R
Santarlasci
Veronica
V
Maggi
Laura
L
Capone
Manuela
M
Frosali
Francesca
F
Rodolico
Gabriella
G
Querci
Valentina
V
Abbate
Gianfranco
G
Angeli
Roberta
R
Berrino
Liberato
L
Fambrini
Massimiliano
M
Caproni
Marzia
M
Tonelli
Francesco
F
Lazzeri
Elena
E
Parronchi
Paola
P
Liotta
Francesco
F
Maggi
Enrico
E
Romagnani
Sergio
S
Annunziato
Francesco
F
D000328:Adult; D000954:Antigens, Surface / Q000235:genetics* / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016022:Case-Control Studies; D002454:Cell Differentiation; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020381:Interleukin-17 / Q000096:biosynthesis*; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism*; D055651:NK Cell Lectin-Like Receptor Subfamily B; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011565:Psoriasis / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation
D000954:Antigens, Surface; C515500:IL23R protein, human; D020381:Interleukin-17; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; C539900:RORC protein, human; D018123:Receptors, Interleukin; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone