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Publication : STAT4 and T-bet control follicular helper T cell development in viral infections.

First Author  Weinstein JS Year  2018
Journal  J Exp Med Volume  215
Issue  1 Pages  337-355
PubMed ID  29212666 Mgi Jnum  J:284613
Mgi Id  MGI:6119043 Doi  10.1084/jem.20170457
Citation  Weinstein JS, et al. (2018) STAT4 and T-bet control follicular helper T cell development in viral infections. J Exp Med 215(1):337-355
abstractText  Follicular helper T (Tfh) cells promote germinal center (GC) B cell survival and proliferation and guide their differentiation and immunoglobulin isotype switching by delivering contact-dependent and soluble factors, including IL-21, IL-4, IL-9, and IFN-gamma. IL-21 and IFN-gamma are coexpressed by Tfh cells during viral infections, but transcriptional regulation of these cytokines is not completely understood. In this study, we show that the T helper type 1 cell (Th1 cell) transcriptional regulators T-bet and STAT4 are coexpressed with Bcl6 in Tfh cells after acute viral infection, with a temporal decline in T-bet in the waning response. T-bet is important for Tfh cell production of IFN-gamma, but not IL-21, and for a robust GC reaction. STAT4, phosphorylated in Tfh cells upon infection, is required for expression of T-bet and Bcl6 and for IFN-gamma and IL-21. These data indicate that T-bet is expressed with Bcl6 in Tfh cells and is required alongside STAT4 to coordinate Tfh cell IL-21 and IFN-gamma production and for promotion of the GC response after acute viral challenge.
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