TY - JOUR
T1 - Early Th1 Cell Differentiation Is Marked by a Tfh Cell-like Transition
AU - Nakayamada, Shingo
AU - Kanno, Yuka
AU - Takahashi, Hayato
AU - Jankovic, Dragana
AU - Lu, Kristina T.
AU - Johnson, Thomas A.
AU - Sun, Hong wei
AU - Vahedi, Golnaz
AU - Hakim, Ofir
AU - Handon, Robin
AU - Schwartzberg, Pamela L.
AU - Hager, Gordon L.
AU - O'Shea, John J.
N1 - Funding Information:
We thank J. Simone and J. Lay for technical help with cell sorting and A.C. Poholek for critical review of the manuscript. This research was supported by the Intramural Research Programs of NIAMS.
PY - 2011/12/23
Y1 - 2011/12/23
N2 - Follicular helper T (Tfh) cells comprise an important subset of helper T cells; however, their relationship with other helper lineages is incompletely understood. Herein, we showed interleukin-12 acting via the transcription factor STAT4 induced both Il21 and Bcl6 genes, generating cells with features of both Tfh and Th1 cells. However, STAT4 also induced the transcription factor T-bet. With ChIP-seq, we defined the genome-wide targets of T-bet and found that it repressed Bcl6 and other markers of Tfh cells, thereby attenuating the nascent Tfh cell-like phenotype in the late phase of Th1 cell specification. Tfh-like cells were rapidly generated after Toxoplasma gondii infection in mice, but T-bet constrained Tfh cell expansion and consequent germinal center formation and antibody production. Our data argue that Tfh and Th1 cells share a transitional stage through the signal mediated by STAT4, which promotes both phenotypes. However, T-bet represses Tfh cell functionalities, promoting full Th1 cell differentiation.
AB - Follicular helper T (Tfh) cells comprise an important subset of helper T cells; however, their relationship with other helper lineages is incompletely understood. Herein, we showed interleukin-12 acting via the transcription factor STAT4 induced both Il21 and Bcl6 genes, generating cells with features of both Tfh and Th1 cells. However, STAT4 also induced the transcription factor T-bet. With ChIP-seq, we defined the genome-wide targets of T-bet and found that it repressed Bcl6 and other markers of Tfh cells, thereby attenuating the nascent Tfh cell-like phenotype in the late phase of Th1 cell specification. Tfh-like cells were rapidly generated after Toxoplasma gondii infection in mice, but T-bet constrained Tfh cell expansion and consequent germinal center formation and antibody production. Our data argue that Tfh and Th1 cells share a transitional stage through the signal mediated by STAT4, which promotes both phenotypes. However, T-bet represses Tfh cell functionalities, promoting full Th1 cell differentiation.
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U2 - 10.1016/j.immuni.2011.11.012
DO - 10.1016/j.immuni.2011.11.012
M3 - Article
C2 - 22195747
AN - SCOPUS:84255178198
SN - 1074-7613
VL - 35
SP - 919
EP - 931
JO - Immunity
JF - Immunity
IS - 6
ER -
