TY - JOUR
T1 - Blimp-1 represses CD8 T cell expression of PD-1 using a feed-forward transcriptional circuit during acute viral infection
AU - Lu, Peiyuan
AU - Youngblood, Benjamin A.
AU - Austin, James J.
AU - Mohammed, Ata Ur Rasheed
AU - Butler, Royce
AU - Ahmed, Rafi
AU - Boss, Jeremy M.
PY - 2014/3
Y1 - 2014/3
N2 - Programmed cell death 1 (PD-1) is an inhibitory immune receptor that regulates T cell function, yet the molecular events that control its expression are largely unknown. We show here that B lymphocyte-induced maturation protein 1 (Blimp-1)-deficient CD8 T cells fail to repress PD-1 during the early stages of CD8 T cell differentiation after acute infection with lymphocytic choriomeningitis virus (LCMV) strain Armstrong. Blimp-1 represses PD-1 through a feed-forward repressive circuit by regulating PD-1 directly and by repressing NFATc1 expression, an activator of PD-1 expression. Blimp-1 binding induces a repressive chromatin structure at the PD-1 locus, leading to the eviction of NFATc1 from its site. These data place Blimp-1 at an important phase of the CD8 T cell effector response and provide a molecular mechanism for its repression of PD-1.
AB - Programmed cell death 1 (PD-1) is an inhibitory immune receptor that regulates T cell function, yet the molecular events that control its expression are largely unknown. We show here that B lymphocyte-induced maturation protein 1 (Blimp-1)-deficient CD8 T cells fail to repress PD-1 during the early stages of CD8 T cell differentiation after acute infection with lymphocytic choriomeningitis virus (LCMV) strain Armstrong. Blimp-1 represses PD-1 through a feed-forward repressive circuit by regulating PD-1 directly and by repressing NFATc1 expression, an activator of PD-1 expression. Blimp-1 binding induces a repressive chromatin structure at the PD-1 locus, leading to the eviction of NFATc1 from its site. These data place Blimp-1 at an important phase of the CD8 T cell effector response and provide a molecular mechanism for its repression of PD-1.
UR - http://www.scopus.com/inward/record.url?scp=84896881497&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84896881497&partnerID=8YFLogxK
U2 - 10.1084/jem.20130208
DO - 10.1084/jem.20130208
M3 - Article
C2 - 24590765
AN - SCOPUS:84896881497
SN - 0022-1007
VL - 211
SP - 515
EP - 527
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 3
ER -