TY - JOUR
T1 - STAT4 and T-bet control follicular helper T cell development in viral infections
AU - Weinstein, Jason S.
AU - Laidlaw, Brian J.
AU - Lu, Yisi
AU - Wang, Jessica K.
AU - Schulz, Vincent P.
AU - Li, Ningcheng
AU - Herman, Edward I.
AU - Kaech, Susan M.
AU - Gallagher, Patrick G.
AU - Craft, Joe
N1 - Funding Information:
J.S. Weinstein was supported in part by National Institutes of Health (NIH) grants K01AR067892-02, UL1 TR001863, and NIH P30 AR053495. Other support came from NIH grants R37 AR40072 and P30 AR053495 (both to J. Craft), the Alliance for Lupus Research (to J. Craft), and NIH grants R01 AR068994 (to J. Craft and P.G. Gallagher) and U54DK106857 (to P.G. Gallagher). The authors declare no competing financial interests.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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-γ. IL-21 and IFN-γ 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-γ, 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-γ 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-γ production and for promotion of the GC response after acute viral challenge.
AB - 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-γ. IL-21 and IFN-γ 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-γ, 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-γ 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-γ production and for promotion of the GC response after acute viral challenge.
UR - https://www.scopus.com/pages/publications/85039970936
U2 - 10.1084/jem.20170457
DO - 10.1084/jem.20170457
M3 - Article
C2 - 29212666
AN - SCOPUS:85039970936
SN - 0022-1007
VL - 215
SP - 337
EP - 355
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 1
ER -