The study investigates the induction and molecular signature of pathogenic T(H)17 cells, which are associated with autoimmune diseases. It is found that TGF-β3, produced by developing T(H)17 cells, is crucial for their pathogenicity when induced by IL-23. TGF-β3-induced T(H)17 cells differ from TGF-β1-induced T(H)17 cells in their functional and molecular characteristics, and exhibit a distinct molecular signature that defines pathogenic effector T(H)17 cells in autoimmune diseases. The study also highlights the role of T-bet, a transcription factor normally associated with Th1 development, in the generation of pathogenic T(H)17 cells. The findings suggest that TGF-β3 may be a potential target for regulating tissue inflammation in multiple autoimmune diseases.The study investigates the induction and molecular signature of pathogenic T(H)17 cells, which are associated with autoimmune diseases. It is found that TGF-β3, produced by developing T(H)17 cells, is crucial for their pathogenicity when induced by IL-23. TGF-β3-induced T(H)17 cells differ from TGF-β1-induced T(H)17 cells in their functional and molecular characteristics, and exhibit a distinct molecular signature that defines pathogenic effector T(H)17 cells in autoimmune diseases. The study also highlights the role of T-bet, a transcription factor normally associated with Th1 development, in the generation of pathogenic T(H)17 cells. The findings suggest that TGF-β3 may be a potential target for regulating tissue inflammation in multiple autoimmune diseases.