This study investigates the role of TGF-β3 in the pathogenicity of T helper 17 (T_H17) cells in autoimmune diseases. TGF-β3, produced by developing T_H17 cells, is dependent on IL-23 and is crucial for the generation of highly pathogenic T_H17 cells. TGF-β3-induced T_H17 cells are functionally and molecularly distinct from TGF-β1-induced T_H17 cells, with a unique molecular signature associated with pathogenic effector T_H17 cells in autoimmune disease. TGF-β3 is endogenously produced by hematopoietic cells and its expression is enhanced by IL-23. TGF-β3-induced T_H17 cells exhibit higher expression of IL-23R and IL-22, and are highly pathogenic, inducing severe autoimmune disease in experimental models. The study also shows that TGF-β3-induced T_H17 cells are functionally distinct from TGF-β1-induced T_H17 cells, with differences in signaling pathways and gene expression profiles. TGF-β3 is involved in the pathogenicity of T_H17 cells, and its expression is regulated by T-bet, a transcription factor normally associated with Th1 development. The study highlights the importance of TGF-β3 in the pathogenicity of T_H17 cells and suggests that TGF-β3 may be a potential therapeutic target for regulating tissue inflammation in autoimmune diseases. The findings indicate that TGF-β3 plays a critical role in the induction of pathogenic T_H17 cells and that its expression is essential for the development of autoimmune disease. The study also reveals that TGF-β3-induced T_H17 cells are closely related to IL-1β-induced T_H17 cells and differ from TGF-β1-induced T_H17 cells. The molecular signature of pathogenic T_H17 cells includes the expression of specific genes and proteins, such as cytokines, chemokines, transcription factors, and effector molecules. The study provides insights into the mechanisms underlying the pathogenicity of T_H17 cells and highlights the importance of TGF-β3 in their development and function. The findings have implications for the treatment of autoimmune diseases, as they suggest that targeting TGF-β3 may be a promising approach for reducing the pathogenicity of T_H17 cells.This study investigates the role of TGF-β3 in the pathogenicity of T helper 17 (T_H17) cells in autoimmune diseases. TGF-β3, produced by developing T_H17 cells, is dependent on IL-23 and is crucial for the generation of highly pathogenic T_H17 cells. TGF-β3-induced T_H17 cells are functionally and molecularly distinct from TGF-β1-induced T_H17 cells, with a unique molecular signature associated with pathogenic effector T_H17 cells in autoimmune disease. TGF-β3 is endogenously produced by hematopoietic cells and its expression is enhanced by IL-23. TGF-β3-induced T_H17 cells exhibit higher expression of IL-23R and IL-22, and are highly pathogenic, inducing severe autoimmune disease in experimental models. The study also shows that TGF-β3-induced T_H17 cells are functionally distinct from TGF-β1-induced T_H17 cells, with differences in signaling pathways and gene expression profiles. TGF-β3 is involved in the pathogenicity of T_H17 cells, and its expression is regulated by T-bet, a transcription factor normally associated with Th1 development. The study highlights the importance of TGF-β3 in the pathogenicity of T_H17 cells and suggests that TGF-β3 may be a potential therapeutic target for regulating tissue inflammation in autoimmune diseases. The findings indicate that TGF-β3 plays a critical role in the induction of pathogenic T_H17 cells and that its expression is essential for the development of autoimmune disease. The study also reveals that TGF-β3-induced T_H17 cells are closely related to IL-1β-induced T_H17 cells and differ from TGF-β1-induced T_H17 cells. The molecular signature of pathogenic T_H17 cells includes the expression of specific genes and proteins, such as cytokines, chemokines, transcription factors, and effector molecules. The study provides insights into the mechanisms underlying the pathogenicity of T_H17 cells and highlights the importance of TGF-β3 in their development and function. The findings have implications for the treatment of autoimmune diseases, as they suggest that targeting TGF-β3 may be a promising approach for reducing the pathogenicity of T_H17 cells.