Molecular Mechanisms Regulating T Helper 1 versus T Follicular Helper Cell Differentiation in Humans

• Main Authors: Nathalie Schmitt, Yang Liu, Salah-Eddine Bentebibel, Hideki Ueno
• Format: Article
• Language: English
• Published: Elsevier 2016-07-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124716308178

IL-12 is important for the differentiation of T follicular helper (Tfh) cells, as well as Th1 cells in humans. Still, how IL-12 signals regulate Tfh versus Th1 cell differentiation remains poorly characterized. Here we aimed to determine the molecular mechanisms that regulate the differentiation and the function of IL-12-stimulated human naive CD4+ T cells. We found that T-bet promoted the expression of CXCR5 in human CD4+ T cells. We provide evidence that T-bet does not strongly inhibit the Tfh cell differentiation program per se but diminishes the functions to provide help to B cells. This study also suggests that IRF4 plays an important role in driving the early differentiation of IL-12-stimulated CD4+ T cells toward Tfh and away from Th1 by inhibiting the expression of Eomesodermin. Thus, the fate of IL-12-stimulated CD4+ T cells is determined through interplay of multiple transcription factors at early stages.