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HL2 Human TH17 cells: An update
Cytokine 56 (2011) 111
Contents lists available at ScienceDirect
Cytokine journal homepage: www.elsevier.com/locate/issn/10434666
Closing Honorary Lecture HL2 Human TH17 cells: An update Sergio Romagnani, Francesco Annunziato, University of Florence, Italy CD4+ T-helper (TH) cells that selectively produce interleukin (IL)-17A (TH17) are thought to be critical for 20 host defense and autoimmunity. Three major dogmas were established, based on initial studies performed in murine models, and initially extrapolated by many researchers to human pathophysiology. First, TH17 cells represent a fixed CD4+ T-cell effector phenotype without any developmental relationship with TH1 cells. Second, TH17 cells are exclusively responsible for pathogenicity in several chronic inflammatory disorders, TH1 cell being instead protective. Finally, TH17 cells originate from naı¨ve TH cells in response to the combined activity of transforming growth factor (TGF)-b and IL-6, whereas in the presence of TGF-b alone the same cells develop into Foxp3+ T regulatory cells. Studies we performed in humans
1043-4666/$ doi:10.1016/S1043-4666(11)00530-8
demonstrated apparent species-specific differences, such as the expression by TH17 cells of the TH1–related transcription factor T-bet, the IL-12-inducible plasticity of TH17 cells into TH1 cells, and the dispensability of TGF-b signaling for their development. More recent studies in mice have led to reassessment of the three above mentioned dogmas regarding the TH17 phenotype, suggesting that murine TH17 cells are not so different than in man after all. Finally, in the last few months, we have demonstrated the existence of a RORC-dependent self regulation of human TH17 cell expansion, probably devoted to reduce their potentially high dangerousness, and we have identified the molecular mechanisms responsible for such regulation. doi:10.1016/j.cyto.2011.07.298
Contents lists available at ScienceDirect
Cytokine journal homepage: www.elsevier.com/locate/issn/10434666
Closing Honorary Lecture HL2 Human TH17 cells: An update Sergio Romagnani, Francesco Annunziato, University of Florence, Italy CD4+ T-helper (TH) cells that selectively produce interleukin (IL)-17A (TH17) are thought to be critical for 20 host defense and autoimmunity. Three major dogmas were established, based on initial studies performed in murine models, and initially extrapolated by many researchers to human pathophysiology. First, TH17 cells represent a fixed CD4+ T-cell effector phenotype without any developmental relationship with TH1 cells. Second, TH17 cells are exclusively responsible for pathogenicity in several chronic inflammatory disorders, TH1 cell being instead protective. Finally, TH17 cells originate from naı¨ve TH cells in response to the combined activity of transforming growth factor (TGF)-b and IL-6, whereas in the presence of TGF-b alone the same cells develop into Foxp3+ T regulatory cells. Studies we performed in humans
1043-4666/$ doi:10.1016/S1043-4666(11)00530-8
demonstrated apparent species-specific differences, such as the expression by TH17 cells of the TH1–related transcription factor T-bet, the IL-12-inducible plasticity of TH17 cells into TH1 cells, and the dispensability of TGF-b signaling for their development. More recent studies in mice have led to reassessment of the three above mentioned dogmas regarding the TH17 phenotype, suggesting that murine TH17 cells are not so different than in man after all. Finally, in the last few months, we have demonstrated the existence of a RORC-dependent self regulation of human TH17 cell expansion, probably devoted to reduce their potentially high dangerousness, and we have identified the molecular mechanisms responsible for such regulation. doi:10.1016/j.cyto.2011.07.298