Vol. 204, No. 8, August 6, 2007 | Francesco Annunziato,1 Lorenzo Cosmi,1 Veronica Santarlasci,1 Laura Maggi,1 Francesco Liotta,1 Benedetta Mazzinghi,1 Eliana Parente,1 Lucia Fili,1 Simona Ferri,1 Francesca Frosali,1 Francesco Giudici,2 Paola Romagnani,1 Paola Parronchi,1 Francesco Tonelli,2 Enrico Maggi,1 and Sergio Romagnani1
The study investigates the phenotypic and functional characteristics of human T helper (Th) 17 cells, a novel subset of CD4+ T cells that are protective against extracellular microbes but are also implicated in autoimmune disorders. The researchers found that Th17 cells, some of which produce both interleukin (IL)-17 and interferon (IFN)-γ (Th17/Th1), are present in the gut of patients with Crohn's disease. These cells exhibit selective expression of IL-23R, CCR6, and the transcription factor RORγt, and share 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 cells also express the Th1-transcription factor T-bet, and stimulation with IL-12 down-regulates RORγt expression and IL-17 production, while inducing IFN-γ. These findings suggest a developmental and/or functional relationship between Th17 and Th1 cells. The study provides the first detailed characterization of human Th17 cells isolated from the gut mucosa of Crohn's disease patients and identifies IL-23R, CCR6, and RORγt as specific markers for Th17 cells. Additionally, the study describes a new subset of IFN-γ-producing Th17 cells that share features with both Th1 and Th17 cells, which has not been previously reported in mice. This novel subset exists in vivo in humans and can be induced in vitro by stimulating Th17 cells with IL-12, raising new questions about the relationship between Th17 and Th1 cells.The study investigates the phenotypic and functional characteristics of human T helper (Th) 17 cells, a novel subset of CD4+ T cells that are protective against extracellular microbes but are also implicated in autoimmune disorders. The researchers found that Th17 cells, some of which produce both interleukin (IL)-17 and interferon (IFN)-γ (Th17/Th1), are present in the gut of patients with Crohn's disease. These cells exhibit selective expression of IL-23R, CCR6, and the transcription factor RORγt, and share 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 cells also express the Th1-transcription factor T-bet, and stimulation with IL-12 down-regulates RORγt expression and IL-17 production, while inducing IFN-γ. These findings suggest a developmental and/or functional relationship between Th17 and Th1 cells. The study provides the first detailed characterization of human Th17 cells isolated from the gut mucosa of Crohn's disease patients and identifies IL-23R, CCR6, and RORγt as specific markers for Th17 cells. Additionally, the study describes a new subset of IFN-γ-producing Th17 cells that share features with both Th1 and Th17 cells, which has not been previously reported in mice. This novel subset exists in vivo in humans and can be induced in vitro by stimulating Th17 cells with IL-12, raising new questions about the relationship between Th17 and Th1 cells.