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

Abstract

CD4+ T-helper (TH) cells that selectively produce interleukin (IL)-17 (TH17) 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, 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 naïve TH cells in response to the combined activity of transforming growth factor (TGF)-β and IL-6, whereas in the presence of TGF-β alone the same cells develop into Foxp3+ T regulatory cells. Studies performed in human 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-β 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 TH17 phenotype, suggesting that studies in humans actually better depicted TH17 cells than initial studies in mice did.