TY - JOUR
T1 - ZEB1, ZEB2, and the miR-200 family form a counterregulatory network to regulate CD8+ T cell fates
AU - Guan, Tianxia
AU - Dominguez, Claudia X.
AU - Amezquita, Robert A.
AU - Laidlaw, Brian J.
AU - Cheng, Jijun
AU - Henao-Mejia, Jorge
AU - Williams, Adam
AU - Flavell, Richard A.
AU - Lu, Jun
AU - Kaech, Susan M.
N1 - Publisher Copyright:
© 2018 Guan et al.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Long-term immunity depends partly on the establishment of memory CD8+ T cells. We identified a counterregulatory network between the homologous transcription factors ZEB1 and ZEB2 and the miR-200 microRNA family, which modulates effector CD8+ T cell fates. Unexpectedly, Zeb1 and Zeb2 had reciprocal expression patterns and were functionally uncoupled in CD8+ T cells. ZEB2 promoted terminal differentiation, whereas ZEB1 was critical for memory T cell survival and function. Interestingly, the transforming growth factor β (TGF-β) and miR-200 family members, which counterregulate the coordinated expression of Zeb1 and Zeb2 during the epithelial-to-mesenchymal transition, inversely regulated Zeb1 and Zeb2 expression in CD8+ T cells. TGF-β induced and sustained Zeb1 expression in maturing memory CD8+ T cells. Meanwhile, both TGF-β and miR-200 family members selectively inhibited Zeb2. Additionally, the miR-200 family was necessary for optimal memory CD8+ T cell formation. These data outline a previously unknown genetic pathway in CD8+ T cells that controls effector and memory cell fate decisions.
AB - Long-term immunity depends partly on the establishment of memory CD8+ T cells. We identified a counterregulatory network between the homologous transcription factors ZEB1 and ZEB2 and the miR-200 microRNA family, which modulates effector CD8+ T cell fates. Unexpectedly, Zeb1 and Zeb2 had reciprocal expression patterns and were functionally uncoupled in CD8+ T cells. ZEB2 promoted terminal differentiation, whereas ZEB1 was critical for memory T cell survival and function. Interestingly, the transforming growth factor β (TGF-β) and miR-200 family members, which counterregulate the coordinated expression of Zeb1 and Zeb2 during the epithelial-to-mesenchymal transition, inversely regulated Zeb1 and Zeb2 expression in CD8+ T cells. TGF-β induced and sustained Zeb1 expression in maturing memory CD8+ T cells. Meanwhile, both TGF-β and miR-200 family members selectively inhibited Zeb2. Additionally, the miR-200 family was necessary for optimal memory CD8+ T cell formation. These data outline a previously unknown genetic pathway in CD8+ T cells that controls effector and memory cell fate decisions.
UR - http://www.scopus.com/inward/record.url?scp=85044841872&partnerID=8YFLogxK
U2 - 10.1084/jem.20171352
DO - 10.1084/jem.20171352
M3 - Article
C2 - 29449309
AN - SCOPUS:85044841872
SN - 0022-1007
VL - 215
SP - 1153
EP - 1168
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 4
ER -