Mouse T helper 17 phenotype: Not so different than in man after all

Abstract: CD4+ T-helper (T(H)) cells that selectively produce interleukin (IL)-17 (T(H)17) are thought to be critical for 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, T(H)17 cells represent a fixed CD4+ T-cell effector phenotype without any developmental relationship with T(H)1 cells. Second, T(H)17 cells are exclusively responsible for pathogenicity in several chronic inflammatory disorders, T(H)1 cell being instead protective. Finally, T(H)17 cells originate from naive T(H) cells in response to the combined activity of transforming growth factor (TGF)-beta and IL-6, whereas in the presence of TGF-beta alone the same cells develop into Foxp3+ T regulatory cells. Studies performed in human demonstrated apparent species-specific differences, such as the expression by T(H)17 cells of the T(H)1-related transcription factor T-bet, the IL-12-inducible plasticity of T(H)17 cells into T(H)1 cells, and the dispensability of TGF-beta signaling for their development. As discussed in this short review, recent studies in mice have led to reassessment of the three above-mentioned dogmas regarding the T(H)17 phenotype, suggesting that studies in humans actually better depicted T(H)17 cells than initial studies in mice did.