TY - JOUR
T1 - Transcription factor STAT3 and type I interferons are corepressive insulators for differentiation of follicular helper and T helper 1 cells
AU - Ray, John P.
AU - Marshall, Heather D.
AU - Laidlaw, Brian J.
AU - Staron, Matthew M.
AU - Kaech, Susan M.
AU - Craft, Joe
N1 - Funding Information:
We thank Shane Crotty for the STAT1 silencing vector. We also thank Steve Reilly for help with RNA-seq analysis and members of the Kaech and Craft laboratories for critical review of the manuscript. This work was supported by the National Science Foundation Graduate Research Fellowship Program under grant 2012099695 (J.P.R.), National Institute of Health grants F32AI094791 (H.D.M), AR40072, AR062842, AI075157, AR053495, AR063942, the Abbvie-Yale Collaboration in Immunobiology, and the Alliance for Lupus Research.
PY - 2014/3/20
Y1 - 2014/3/20
N2 - Follicular helper T (Tfh) cells are required for the establishment of T-dependent B cell memory and high affinity antibody-secreting cells. We have revealed herein opposing roles for signal transducer and activator of transcription 3 (STAT3) and type I interferon (IFN) signaling in the differentiation of Tfh cells following viral infection. STAT3-deficient CD4+ Tcells had a profound defect in Tfh cell differentiation, accompanied by decreased germinal center (GC) B cells and antigen-specific antibody production during acute infection with lymphocytic choriomeningitis virus. STAT3-deficient Tfh cells had strikingly increased expression of a number of IFN-inducible genes, in addition to enhanced T-bet synthesis, thus adopting a T helper 1 (Th1) cell-like effector phenotype. Conversely, IFN-αβ receptor blockade restored Tfh and GC B cell phenotypes in mice containing STAT3-deficient CD4+ Tcells. These data suggest mutually repressive roles for STAT3 andtype I IFN signaling pathways in the differentiation of Tfh cells following viral infection.
AB - Follicular helper T (Tfh) cells are required for the establishment of T-dependent B cell memory and high affinity antibody-secreting cells. We have revealed herein opposing roles for signal transducer and activator of transcription 3 (STAT3) and type I interferon (IFN) signaling in the differentiation of Tfh cells following viral infection. STAT3-deficient CD4+ Tcells had a profound defect in Tfh cell differentiation, accompanied by decreased germinal center (GC) B cells and antigen-specific antibody production during acute infection with lymphocytic choriomeningitis virus. STAT3-deficient Tfh cells had strikingly increased expression of a number of IFN-inducible genes, in addition to enhanced T-bet synthesis, thus adopting a T helper 1 (Th1) cell-like effector phenotype. Conversely, IFN-αβ receptor blockade restored Tfh and GC B cell phenotypes in mice containing STAT3-deficient CD4+ Tcells. These data suggest mutually repressive roles for STAT3 andtype I IFN signaling pathways in the differentiation of Tfh cells following viral infection.
UR - http://www.scopus.com/inward/record.url?scp=84896372779&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2014.02.005
DO - 10.1016/j.immuni.2014.02.005
M3 - Article
C2 - 24631156
AN - SCOPUS:84896372779
SN - 1074-7613
VL - 40
SP - 367
EP - 377
JO - Immunity
JF - Immunity
IS - 3
ER -