Phenotypic and functional features of human Th17 cells.
T helper (Th) 17 cells represent a novel subset of CD4+ T cells that are protective against extracellular microbes, but are responsible for autoimmune disorders in mice. However, their properties in humans are only partially known. We demonstrate the presence of Th17 cells, some of which produce both interleukin (IL)-17 and interferon (IFN)-gamma (Th17/Th1), in the gut of patients with Crohn's disease. Both Th17 and Th17/Th1 clones showed selective expression of IL-23R, CCR6, and the transcription factor ROR gamma t, and they exhibited similar functional features, such as the ability to help B cells, low cytotoxicity, and poor susceptibility to regulation by autologous regulatory T cells. Interestingly, these subsets also expressed the Th1-transcription factor T-bet, and stimulation of these cells in the presence of IL-12 down-regulated the expression of ROR gamma t and the production of IL-17, but induced IFN-gamma. These effects were partially inhibited in presence of IL-23. Similar receptor expression and functional capabilities were observed in freshly derived IL-17-producing peripheral blood and tonsillar CD4+ T cells. The demonstration of selective markers for human Th17 cells may help us to understand their pathogenic role. Moreover, the identification of a subset of cells sharing features of both Th1 and Th17, which can arise from the modulation of Th17 cells by IL-12, may raise new issues concerning developmental and/or functional relationships between Th17 and Th1.
Annunziato
Francesco
F
Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders (DENOTHE), University of Florence, Florence 50134, Italy.
Cosmi
Lorenzo
L
Santarlasci
Veronica
V
Maggi
Laura
L
Liotta
Francesco
F
Mazzinghi
Benedetta
B
Parente
Eliana
E
Filì
Lucia
L
Ferri
Simona
S
Frosali
Francesca
F
Giudici
Francesco
F
Romagnani
Paola
P
Parronchi
Paola
P
Tonelli
Francesco
F
Maggi
Enrico
E
Romagnani
Sergio
S
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D049109:Cell Proliferation; D003001:Cloning, Molecular; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism*
C106311:CCR6 protein, human; C515500:IL23R protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D018664:Interleukin-12; D007371:Interferon-gamma