Induction and molecular sigNature of pathogenic TH17 cells
Interleukin 17 (IL-17)-producing helper T cells (TH17 cells) are often present at the sites of tissue inflammation in autoimmune diseases, which has led to the conclusion that TH17 cells are main drivers of autoimmune tissue injury. However, not all TH17 cells are pathogenic; in fact, TH17 cells generated with transforming growth factor-β1 (TGF-β1) and IL-6 produce IL-17 but do not readily induce autoimmune disease without further exposure to IL-23. Here we found that the production of TGF-β3 by developing TH17 cells was dependent on IL-23, which together with IL-6 induced very pathogenic TH17 cells. Moreover, TGF-β3-induced TH17 cells were functionally and molecularly distinct from TGF-β1-induced TH17 cells and had a molecular signature that defined pathogenic effector TH17 cells in autoimmune disease.
Authors: Youjin Lee, Amit Awasthi, Nir Yosef, Francisco J Quintana, Sheng Xiao, Anneli Peters, Chuan Wu, Markus Kleinewietfeld, Sharon Kunder, David A Hafler, Raymond A Sobel, Aviv Regev & Vijay K Kuchroo
Influence Factor: 21.506
Citation: Nat Immunol 13, 991-999 (2012).