TY - JOUR
T1 - PU.1 plays a pivotal role in dendritic cell migration from the periphery to secondary lymphoid organs via regulating CCR7 expression
AU - Yashiro, Takuya
AU - Takeuchi, Hiromi
AU - Nakamura, Shusuke
AU - Tanabe, Atsushi
AU - Hara, Mutsuko
AU - Uchida, Koichiro
AU - Okumura, Ko
AU - Kasakura, Kazumi
AU - Nishiyama, Chiharu
N1 - Publisher Copyright:
© FASEB
PY - 2019/10/1
Y1 - 2019/10/1
N2 - C-C chemokine receptor type 7 (CCR7) is essential for migration of dendritic cells (DCs) to draining lymph nodes. PU.1/Spi1 is a transcription factor playing a critical role in the gene regulation of DCs. PU.1 knockdown decreased the expression of CCR7 in bone marrow–derived DCs and subsequently attenuated migration in vitro and in vivo. Reporter assays, EMSA, and chromatin immunoprecipitation assays revealed that PU.1 binds to the most proximal Ets motif of the Ccr7 promoter, which is involved in transcriptional activation. The CCR7 expression level, which was higher in the programmed cell death 1 ligand 2 (PD-L2)+ population than in the PD-L2− population and was markedly suppressed by TGF-β treatment, coincided with the binding level of PU.1 to the Ccr7 promoter. The PU.1 binding level in CCR7high mesenteric lymph nodes DCs was higher than in other DC subtypes. The involvement of PU.1 in the expression of the CCR7 gene was also observed in human DCs. We conclude that PU.1 plays a pivotal role in DC migration by transactivating the CCR7 gene via the Ets motif in the promoter in both humans and mice.—Yashiro, T., Takeuchi, H., Nakamura, S., Tanabe, A., Hara, M., Uchida, K., Okumura, K., Kasakura, K., Nishiyama, C. PU.1 plays a pivotal role in dendritic cell migration from the periphery to secondary lymphoid organs via regulating CCR7 expression. FASEB J. 33, 11481–11491 (2019). www.fasebj.org.
AB - C-C chemokine receptor type 7 (CCR7) is essential for migration of dendritic cells (DCs) to draining lymph nodes. PU.1/Spi1 is a transcription factor playing a critical role in the gene regulation of DCs. PU.1 knockdown decreased the expression of CCR7 in bone marrow–derived DCs and subsequently attenuated migration in vitro and in vivo. Reporter assays, EMSA, and chromatin immunoprecipitation assays revealed that PU.1 binds to the most proximal Ets motif of the Ccr7 promoter, which is involved in transcriptional activation. The CCR7 expression level, which was higher in the programmed cell death 1 ligand 2 (PD-L2)+ population than in the PD-L2− population and was markedly suppressed by TGF-β treatment, coincided with the binding level of PU.1 to the Ccr7 promoter. The PU.1 binding level in CCR7high mesenteric lymph nodes DCs was higher than in other DC subtypes. The involvement of PU.1 in the expression of the CCR7 gene was also observed in human DCs. We conclude that PU.1 plays a pivotal role in DC migration by transactivating the CCR7 gene via the Ets motif in the promoter in both humans and mice.—Yashiro, T., Takeuchi, H., Nakamura, S., Tanabe, A., Hara, M., Uchida, K., Okumura, K., Kasakura, K., Nishiyama, C. PU.1 plays a pivotal role in dendritic cell migration from the periphery to secondary lymphoid organs via regulating CCR7 expression. FASEB J. 33, 11481–11491 (2019). www.fasebj.org.
KW - Ets
KW - MLN
KW - PD-L2
KW - TGF-β
KW - chemokine receptor
UR - http://www.scopus.com/inward/record.url?scp=85072718639&partnerID=8YFLogxK
U2 - 10.1096/fj.201900379RR
DO - 10.1096/fj.201900379RR
M3 - Article
C2 - 31314592
AN - SCOPUS:85072718639
SN - 0892-6638
VL - 33
SP - 11481
EP - 11491
JO - FASEB Journal
JF - FASEB Journal
IS - 10
ER -